Per wiki policy, Spoilers Off applies here and all spoilers are unmarked. You Have Been Warned.

Let's just say there's a reason why this game is often hailed as one of the scariest games in the franchise.

• The X themselves are actually pretty frightening creatures when you think about it. A creature that can infect a host, kill them, and mimic them down to the cellular level with ALMOST no way of identifying that you're looking at a fake? Pure Paranoia Fuel at its finest...
  • While it's pretty much a foregone conclusion that you're not going to be able to prevent the spread of the X making it to the various sectors of the station, the sheer perseverance of the creatures is frightening. You kill the first boss and find they've already made it to the first sectors. Deal with Sector 2 and unlock the very first security doors, they invade more of the station, and it keeps going like this with you unlocking doors and them immediately invading the newly open areas. While you have no other choice but do this in order to progress anywhere yourself, it's actually rather frightening how persistent the X is about spreading. Imagine if they had escaped the facility...
  • The fact that these creatures absorb a host, kill them, and can mimic them is bad enough, but notice what they do to the physiology of the creature they infect. For example, compare this image◊ of the Hornoad from Metroid II: Return of Samus with this◊. Not only does the X seem to mimic a host, it seems capable of changing them into something significantly more terrifying and monstrous than before.
  • The fact that because the X parasites can obtain the knowledge of their victims, they can potentially build spaceships and infect the whole galaxy at an exponential rate. The X themselves are pretty much straight transplants of the creature from The Thing (1982) and the game is not shy about this particular piece of influence.
  • Your first venture into Sector 6 has Adam warn you about X parasites who purposefully exposed themselves to Sector 5's sub-zero temperatures, knowing that as part Metroid, Samus is now severely weak to cold, and will actively suicide into you on sight in an attempt to destroy you. A case of It Can Think mixed in with the horror that these creatures are now royally pissed and intent on killing you off however it can now.
    AI Adam: Be careful, Samus. They are hunting you, now.
• The close-up reveal of the SA-X's face, complete with ghastly white, glowing eyes casting dark shadows on the rest of it. It looks absolutely wrong coming from the visor of what looks like the classic Power Suit.
  • SA-X is Nightmare Fuel all by itself. It mimics a full-power Samus, so can kill her easily with the Ice Beam, Screw Attack and Super Missiles (and even other endgame-level weapons, like the Power Bomb) if it catches her and can't even be slowed if you try to fight it head-on, and the theme for when SA-X is around is... unsettling, to say the least. It speaks volumes when Samus herself goes into detail about how much of a threat it is when discussing it, fearing the possibility of it getting loose and turning its attention to civilization:
    The SA-X. An enemy with my strongest abilities. But does it have reason? Probably not. It's just a killing machine. In my current state, I can't face it head-on. The SA-X is me, only heartless. I must stop it before it learns its potential and threatens the universe...
  • The sound of its footsteps invoke the worst kind of terror. This thing can, and will, kill you easily. The only way to survive is to run for your life. Extra points for the sound effects here: Samus herself has audible footsteps that sound rather light as she jogs briskly. The SA-X? It stalks you, with metallic echoes resonating with each deliberate footfall, and if you are spotted, the deliberate pacing will turn into a brisk tapping as it sprints for you.
  • If you play Metroid Fusion enough, you can hear SA-X coming just by listening to the theme. Its presence invades your subconscious.
  • Late into the game, the SA-X is found in the restricted laboratory area, fighting off larval Metroids and thankfully not paying attention to you. However, this causes a self-destruct sequence that will detach the restricted area from the rest of the research station and make it explode. Once you haul ass out of there, you'll likely be delighted to know that the SA-X didn't follow, and exploded with the rest of the restricted area. What you certainly won't be delighted to hear, however, is that the SA-X had asexually reproduced, and now there are no less than ten of them on the station. You know, because one of the bastards wasn't bad enough! Thank god that this ends up being a case of Gameplay and Story Segregation, and you won't encounter any of them until you fight the SA-X as a boss later on, otherwise a lot of people wouldn't be able to finish the game from sheer fright alone...
  • Speaking of said fight, when you battle the SA-X as the penultimate boss, it does not disappoint- dishing out attacks just like yours and flying through the air with horizontal Screw Attacks. When you take out enough of its health, the SA-X falls to one knee and it looks like it might be over. Then it turns into something that Lovecraft would've been proud to come up with.
• Nightmare, Nightmare, Nightmare. While the SA-X might hold the reputation as Fusion's scariest foe, if not in the whole franchise, Nightmare comes a pretty close second. This... thing is a massive, mechanical, floating monstrosity that can alter gravity at will thanks to the manipulator on its underside. Just look at it◊! Even the music that plays while fighting it is unsettling.
  • Think that it's not scary enough? As you fight it, its "face" begins to leak a green fluid from its eyeholes, in a way that makes it look like it's crying. Keep blasting at its face, and it will explode... revealing Nightmare's true face◊ underneath. Good lord.
  • And to top it all off, as you damage it, its face starts to slough off, revealing nothing but empty space where its skull should be. How is this thing even alive?
  • Did we mention that this thing was created by the Galactic Federation - i.e, the guys on your side (or at least the guys that were before you find out their motives)? The fact that the "good guys" have this thing and not the bad guys is pretty unsettling.
    • Made by the Galactic Federation or not, just consider for a bit why Nightmare was even created - It was made as a military weapon. Just imagine, you're fighting the Federation, and they suddenly unleash this ungodly monster that immediately begins increasing gravity, making it impossible to move, and ripping your fellow soldiers apart with ease (all while "crying" green ooze), and when it comes for you, the last thing you see before you die is that goddamn face. Have fun with that thought when you go to sleep tonight.
  • Nightmare also gets much more of an introduction than most of the other bosses, giving the player sufficient time to build up their own unease. During Samus's first trip to Sector 5, the player enters an enormous windowed room near the start of the Sector and every few seconds a huge silhouette flies past, causing the entire room to shake every time it does so (which you just know you're going to wind up face-to-face with eventually). Much later in the game, there's an explosion in Sector 5 and when Samus goes to investigate, all the windows in the room are shattered and Nightmare is nowhere to be found.
  • It's worth noting that Nightmare's movements in its boss fight are slow, steady, and really not that rapid, if a bit jerky, but when you see its shadow in Sector 5 early on, it's blitzing around in an almost directionless frenzy. While this can be seen as it rampaging, the movements can also be seen as it panicking or fleeing. This hulking, horrifying mechanical monster may very well be terrified at the threat the X parasites pose to it, desperately trying to avoid being consumed by them... an effort that ultimately fails.
• The Galactic Federation's motives. They denied Samus from blowing up the space station so they could capture a live specimen of SA-X to use as a controlled biological weapon, despite the 100% risk of it killing them all, then raising them as shapeshifting monstrosities, and then multiplying, spreading across the galaxy, eventually the universe, destroying all civilization. Weyland-Yutani would be proud of these guys.
  • In fact, this knowledge brings up a lot of unanswered questions as both this game and Metroid: Other M are the only ones in the series to show that the Federation isn't entirely on the same side as you. Why are they doing this to begin with? Have they become so desperate for extra power that they feel they need to rely on horrific monsters in order to protect themselves and the galaxy? If that's the case, then what has made them so desperate? Or were the observations about Metroids in Super Metroid being able to vastly benefit humanity something of the start to their descent into a dark mindset cause of a lust for that power? And if so, does that mean that this game is the continuation of their lust for power to put them as the lead authority in the galaxy? Unfortunately, as of this point there are no answers to any of those questions, but the implications that each of those possibilities present are not good. At all.
    Samus: As soon as the Federation ships land, the X will overwhelm them and absorb the knowledge and power of their occupants. The X are just waiting for the hunt to begin, and then they'll spread across the universe. Galactic civilization will end. The X hunger for form, knowledge, and power. They mimic these perfectly. But they cannot copy the soul. They're single-minded, instinctively seeking to increase in number. They're a plague, and the Federation underestimates their threat. The X must not leave here. I must destroy them all before the Federation arrives. This station has a self-destruct mechanism. I must use it to destroy the X here and on the planet. I must send them to oblivion. Them, the station, and myself, if I have to.
  • In terms of continuity, this game actually takes place after Metroid: Other M, and that game, as mentioned above, also involved a secretive GF project with severe moral ambiguity as to their motives and intentions. One of the main criticisms of that game was that, outside of a handful of events, Samus's presence on the Bottle Ship had little to no overall impact on the ending of that story given the ending featured the Galactic Federation showing up at the last minute to take over the situation and dismiss Samus. The events on the Bottle Ship claimed the lives of Adam Malkovich, Samus's father figure and mentor, and his entire platoon minus Anthony. Think about that in relation to this game now and finding that the Federation is once more involved in shady projects when the last one claimed the lives of innocent men and the person she trusted the most in the whole galaxy, all the while she couldn't really do anything to help anyone... and you wonder if she starts getting flashes of PTSD at this point. Maybe it's no wonder that, as the AI-Adam points out, she seems so hasty to blow herself up to end the threat.
    • And one more nugget, just to make that point harsher? A Red Herring of Other M was that Adam Malkovich was involved with and supported the project from the start, calling into question the motives of her own mentor. Cue this game and the AI-Adam, who she's slowly begun to imprint on in memory of the real Adam, is actively trying to keep Samus in the dark about the new Metroid breeding program and even locks her in a Navigation Room when the objective shifts to the Federation attempting to capture an SA-X, explaining why its tone starts getting harsher and more reprimanding the more the mission goes off the rails and Samus starts entering even more secure areas. Thankfully it eventually sides with Samus and aids her in destroying the station and the X on board by the end, but still...
• A disturbing detail happens after taking care of Zazabi in Sector 2. All the larval Zeroes you've encountered on the way seem to be a colorless, impenetrable state, but after the first SA-X encounter, it becomes clear that they're evolving inside cocoons, with some small movements making it look like they could emerge any second. Even after they finally become Kihunters, the cocoons' skeletal-looking remains are still present throughout.
• At one point, rapid plant overgrowth causes the station's power to go out completely, disabling everything, including the save points. A save point can be seen as something of a perch a player can go back onto if things get scary. Now you don't even have that to comfort you, never mind that it gives the SA-X the perfect cover to show up at any moment and eviscerate you while you're stumbling around in the dark. Thankfully, it doesn't.
• Considering how much your AI companion holds your hand through the first ~2/3 of the game, it's actually quite unsettling when you start doing in-universe Sequence Breaking that leaves him surprised. Shortly after the aforementioned power outage, it suddenly becomes very clear that you have entirely jumped the rails; the sense of exposure that realization grants is surprisingly jarring.
• The "Emergency in Sector 3" section of the game, where, out of nowhere, the whole area starts flashing red while frenzied music plays, overlaid with a creepy robotic voice repeating EMERGENCY IN SECTOR 3! EMERGENCY IN SECTOR 3! From there, you are only given 6 minutes until the entire station explodes.
• Serris, the boss of Sector 4, can be pretty scary all on its own, basically being a super-fast water snake-dragon-centipede thing. Seeing what happened to the real Serris is just plain unsettling, though. You're informed by Adam that Serris is contained in a breeding tank located just before the actual boss room. "Environmental Disquiet" starts as soon as you enter the room and you see that Serris, this big nasty monster that Adam warned you about, has been reduced to nothing more than the skeleton now lying at the bottom of the tank.
• At the very beginning of the game, you can enter a cold storage room where you can see the frozen remains of none other than Ridley. After the power goes out, you have to pass through this room again and come face-to-face with the long-dead monster. Then he crumbles into pieces as a Core-X floats away, having stolen Ridley's DNA. Then, almost at the very end of the game, you find Ridley again at the bottom of a tall room, only now he looks like he's been dipped in molten metal and left out to dry. Then, his eyes start to glow. The characteristic "pixelization" of the X parasites covers his entire body, and we meet Neo-Ridley◊, becoming twice the size that he was before and roaring loud enough to lag the game. Yikes!
• Something that doesn't get brought up enough with regards to Fusion is the overall sound design. The game's soundtrack and ambient sounds ratchet up the dread like no other Metroid game before it. The music has a much more dramatic and heart-pounding tone that constantly makes your heart tense up as you navigate the desolate station while creature sounds and definitely the sounds the bosses make can induce rampant panic attacks that numb your focus and make you react instinctively instead of tactically because you just want it to go away. Play this game with your headphones on and in the dark and it is grade-A Paranoia Fuel.
• The setting for this game is unlike any other Metroid game. Samus is no stranger to lone wolfing it but due to the circumstances, this game truly makes you feel dreadfully alone and exposed. Everyone on the research station is dead and it's overrun with barely-understood parasites, one of which is basically a walking armory. In other Metroid titles at least Samus feels like she's on somewhat equal footing with her foes but in this game you almost constantly feel woefully underequipped, having to resort to sneaking around and avoiding situations instead of confronting them head on. You're in their house. Plus every so often something will go haywire and send the unsettling slow pace into frantic overdrive and you won't know what's wrong or what to do for the first few minutes.
  • The overall situation from beginning to end as the station rapidly deteriorates. At first, it's a simple deal of certain sectors being locked off with higher security measures than others, but the more the X swarm the station and actively try its hardest to impede Samus, several sectors change drastically as areas are destroyed and ripped apart, and even the creatures themselves evolve into more dangerous forms to try and kill you. Even as Samus recovers her core abilities, you'll still feel like you're trying to catch up to the difficulty curve as the X literally rip the station to shreds trying to kill you.
• SIXTY SECONDS TILL IMPACT.
• The premise has been mentioned already, but minus one detail...this is the weakest Samus has ever been. Oh sure, the first game had its moments, but here, Samus has had NO time to recover from a near-death experience before being sent to BSL. Adam's statistical breakdown when she arrives says she's only at 10% battle capacity, with that being her odds of survival. Samus is in far more dangerous territory, with a species she's having to learn about on the fly, taking increased damage as her suit has been basically carved up from the badass warrior armor down to what seems almost form fitting and significantly less protective...need we go on? Essentially, the odds are SIGNIFICANTLY stacked against you from the minute you start the game and unless you manage to find over half the secret items hidden away, it doesn't get any better.
• The SA-X does not relinquish its power so easily. It flees on you. Then, Samus gets the dark idea to crash the space station so not one X survives. After all this, you think the game is done and all you have to do is escape in 3 minutes. Then, you get to the hangar, where there is a discarded membrane. It turns out SA-X wasn't the worst threat in the game. It's the final boss, an Omega Metroid, freshly out of its cocoon. While the game had hinted that a Metroid managed to get loose from the restricted laboratory, given that you find discarded Metroid membranes elsewhere, the sheer speed at which it evolves into an Omega Metroid comes as a huge surprise, and the clock is ticking toward oblivion. The beast takes one swipe at Samus and she immediately drops to 1 hit point. Luckily, SA-X morphs into Samus one more time to hit its weak spot and then Samus can reclaim her final ability and full power to even the playing field.