- After the Metroids were considered to be wiped out, the deadlier X parasites attack Samus. She is given a new suit after her near-death experience and returns to an empty Galactic Federation station, where something seems out of place.
- After the fall of Zebes (Super Metroid), Samus and a research team from Galactic Federation travel to SR388, only to find more trouble. After the Metroids were considered to be wiped out, their prey, the deadlier X parasites, attack Samus. Samus is, once again, given a new suit after her near-death experience. She then returns to an empty Galactic Federation station, where something seems out of place...—Dana B
- Several years after the destruction of the planet Zebes (Super Metroid (1994)), Samus Aran finds herself back on the surface of planet SR388, which she once freed from the dominance of the Metroids (Metroid II: Return of Samus (1991) or the remake Metroid: Samus Returns (2017)). The Federation has hired Biological Space Labs (BSL) to investigate the planet, and collect biological samples that can tell how the ecosystem is doing without the Metroids on top of the food chain. Because of her experience on the planet, Samus was asked to give BSL assistance.
The planet is slowly recovering, and many species previously unseen have emerged. During a routine collection trip, Samus defends herself against a native creature. Upon dying, the creature suddenly reforms into an amoeba-like creature that she has never seen before. It quickly infiltrates her suit. Seeing no immediate harm in this, Samus returns to her ship in order to return to the BSL research ship that is orbiting SR388. But during her flight, something unexpected happens: she suddenly feels sick and loses consciousness. Her ship stars to drift away into an asteroid belt. Luckily, the ship automatically jettisons Samus' body in an auto-escape pod before it crashes. The scientist from the research ship retrieve the pod and bring Samus to Galactic Federation HQ, where they establish that the infectious life form, dubbed the X parasite, has rapidly multiplied and is infecting her central nervous system. Samus is in a deep coma, while the parasites have also spread to the biological parts of her Power Suit. The suit has become so fused with her body that the scientist have to surgically remove parts of it. The removed parts, as well as several life forms that have been captured on SR388, are sent for further study to an enormous BSL research station that is also in orbit around SR388. Nevertheless, as nothing can be done against the infection in her nervous system, Samus is given a minimal chance of survival. One of the scientists suddenly thinks of a desperate measure: if Metroids are so deadly, then perhaps Metroid cells are able to defeat the X on a cellular level. Fortunately, some cells of the infant Metroid that was spared by Samus in Metroid II: Return of Samus/Metroid: Samus Returns have been preserved, which are used to create a vaccine. The therapy works perfectly and the X parasites disappear from Samus' body: the infant has saved Samus' life for the second time. However, her cells start to take characteristics of the Metroid cells, which drastically changes her appearance.
Immediately after Samus regains consciousness, Federation HQ receives a distress call from the BSL station; a sudden explosion in the Quarantine bay has rocked the facility. Samus can hear the screams from the com receiver from the infirmary, and knows instinctively that something very bad is happening there. She is sent back to the BSL research station to investigate. The Federation gives Samus the use of another ship, under the condition that she follow the orders of the new ship's computer that was installed in it, to which she begrudgingly concedes. She never liked taking orders, especially from a computer.
Samus quickly flies to the station and lands in the Docking Bay. The BSL station is an enormous structure, consisting of six large connected pods, constructed around and inside a giant meteor. Through Navigation Rooms spread throughout the station, Samus can keep in touch with her ship's computer. This computerized CO uses a similar tone as her former commander, Adam Malkovich; she therefore decides to nick-name it Adam. Samus quickly makes a startling discovery: the creatures that were captured on SR388 and brought back are, in fact, infected with X parasites. The parasites have the remarkable ability to sample their host's genetic information before they kill it, and mimic them. They have already started to spread and infect other creatures. However, Samus now appears immune to the parasites: it finally becomes clear that by destroying the Metroids, Samus has inadvertently given the X the opportunity to thrive again. Luckily, Samus' fusion with the Metroid infant's cells enable her to safely absorb the free-floating X parasites for extra health and ammunition. Unfortunately, it also gives her the Metroid's susceptibility to cold. She needs to strengthen up first. However, the X have already infiltrated the breeding environments in the simulation of the SR388 habitat, aided by something unknown. The parasites have even started to mimic Alpha Metroids, Space Pirates and Chozo statues, but by defeating the larger specimens and absorbing the parasites, she recovers more and more weapons and suit upgrades.
Adam eventually learns the saboteur's identity: it is an X parasite mimicking Samus herself! This SA-X has spawned from an infected suit part and has escaped the Quarantine Bay by causing the initial explosion; this explosion set free all the other parasites as well. As the SA-X is a copy of Samus at full power, there is no way she can defeat it in her current fragile state. To make matters worse, all of Samus' efforts to open doors inside the habitats also open the doors for the X to spread to other habitats. A series of destroyed doors signify that the SA-X is deliberately trying to impede Samus' progress, and the discovery that the SA-X is also destroying Data Rooms to prevent Samus' weapons recovery makes it very clear that SA-X is a calculating, intelligent, and therefore even more dangerous species. As Samus goes on her way, she has several run-ins with and narrow escapes from SA-X, which is actively searching for her. What she doesn't know is that Adam is secretly speaking with an unidentified man: they are obviously keeping something from her.
In a desperate measure to stop Samus, SA-X disables the main boiler's cooling unit. This could trigger the auto-destruct explosives and easily destroy the entire station, so Samus has to act quickly and is narrowly able to avoid the catastrophe; the X has mimicked a crew member, and thereby also absorbed the memory and knowledge about the cooling unit. Adam ponders why a clearly intelligent and self-preserving species like the X would try to destroy the station and thereby kill itself; he hypothesizes that the X parasites in the station would try to kill Samus at any cost, even by sacrificing itself, because she has now become such a large threat to X parasites elsewhere.
While investigating life signs on the Habitation Deck, Samus discovers some old friends: the friendly creatures she met on Zebes, who had taught her some techniques to escape. It is her turn to set them free so they can get out. While returning to her ship for an important update from Adam, Samus gets stuck in an elevator when the power suddenly goes down. She uses an old access way to get out, ending up in a room with a frozen Ridley. The old fiend falls apart, after which an X-parasite flies out of him; he had been infected as well. Another crisis is yet announced: an infected military weapon called the Nightmare was causing major damage to the station. She destroys it, goes on to restore main power, and further roaming through the station yields more unexpected upgrades to her suit. However, her searches lead her into a Restricted Zone within the station, where she makes a startling discovery: there is a lab there where all types of Metroids are kept in stasis! An SA-X also enters the lab and starts killing Metroids, which leads to an auto-destruct sequence being initiated. Samus barely manages to get to safety before the lab is ejected from the station and explodes, taking the SA-X with it.
Adam reproaches Samus for entering the forbidden zone against orders: he tells her that the Federation has been secretly working on a Metroid breeding program for peaceful purposes. The SR388 habitat has been built specifically to raise them, and research has revealed how they could be grown into Omega Metroids in matter of days. In the meanwhile, the SA-X has multiplied itself, and no less than 10 specimen are currently looking for Samus, so she has to escape from the station. On her way, she has to destroy an X-parasite that shape-shifts into a grotesque version of Ridley. When she is near the exit, Samus learns from Adam that the Federation has started to take an interest in the scientific potential of the X-parasites themselves, especially the SA-X. The Federation has been actively trying to withhold necessary weapons upgrades from Samus so she cannot destroy them. The computer has been ordered to keep Samus confined until the Federation ships arrive.
Knowing that the Federation could never subdue the X, Samus fears that the X will easily infect their scientists and absorb their knowledge, using it to spread throughout the entire Galaxy and destroy every civilization. She decides she needs to use the station's self-destruct mechanism to destroy all X on board and on the planet SR388 below. In a desperate attempt to appeal to the computer to release her, she addresses it as Adam. Getting curious, the computer hears Samus' story about the real Adam and how he would do the right thing to safe the galaxy, even sacrificing his own life. Quite unexpectedly, the machine seems to comprehend, releasing Samus and advising her how to start up the self-destruct system. To Samus' amazement, he even tells her how to initiate the station's propulsion system, thereby including the planet below in the station's evaporation field, which will destroy SR388. He finally addresses her as 'Lady', just like the real Adam always did. Samus assumes that Adam's military mind must have been used for the computer's personality.
Samus goes up to the Operation Platform, but before she can alter the station's course, an SA-X enters the room, after which a fierce battle ensues. Despite being almost equally matched, Samus has the benefit of years of battle experience, and succeeds in weakening her rival, to the point where it mutates into a grotesque monstrosity, which Samus finally defeats. However, its parasite inside manages to get away. Samus enters the Operation Room, where she activates the ship's propulsion system. While the countdown starts, she runs towards the hangar bay. But when she gets there, her ship is gone. To her horror, the only thing she sees laying there is the giant shell of an adult Metroid. It doesn't take long for a huge Omega Metroid to appear. It puts her to her knees with a single slash of its razor-sharp claw. But then, the X-parasite enters and reforms into an SA-X. It starts taking on the Metroid, but the SA-X is no match for the huge beast either. Samus quickly absorbs the released X parasite, upgrading her suit and weapons to full power, which is enough to destroy the monster. Her ship reappears and she boards it, getting away in time before the station descends into the planet, and both are destroyed in a giant explosion.
Samus fears that the people will hold her responsible for the destruction of the station and all of the X, but Adam assures her that one of them will see the logic of her decision, and that she has done the right thing. While wondering how her ship was able to steer back into the hangar by itself, Adam points out he got help from the Zebes creatures, who are peacefully sleeping in the back of the ship.
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