A genetically enhanced next-generation Special Forces unit commanded by FOXHOUND leads an armed uprising on a remote island in Alaska's Fox Archipelago. This island, codenamed Shadow Moses, is the site of a nuclear weapons disposal facility. The forces that seized this island have acquired the nuclear-capable mecha Metal Gear REX, and are threatening the U.S government with a nuclear reprisal if they do not receive the remains of the "legendary mercenary" Big Boss within 24 hours.
Solid Snake is forced out of retirement and is dispatched at the request of Colonel Roy Campbell to penetrate the terrorists' defenses and neutralize the threat. Snake is also ordered to locate hostages DARPA Chief Donald Anderson, and ArmsTech president Kenneth Baker. Colonel Campbell's daughter, at the time believed to be niece, Meryl Silverburgh, is also held captive in the facility after refusing to take part in the uprising. Snake enters the facility via an air vent and eventually locates the DARPA Chief in a cell. He informs Snake of the new Metal Gear REX unit housed at the facility and how he can prevent it from being launched using a secret detonation override code, but then suddenly dies of what appears to be a heart attack. Meryl, who is held in adjoining cell, manages to break out and assists Snake in his escape as enemy soldiers are alerted to his presence. Snake then finds the other hostage, Kenneth Baker. Whilst attempting to free Baker, Snake is confronted by Revolver Ocelot who challenges Snake to a gunfight, which is interrupted by a mysterious cyborg ninja who cuts off Ocelot's right hand. Baker briefs Snake on the Metal Gear project and advises him to contact Meryl, whom he gave a PAL card that could be used to prevent the launch, but like the DARPA Chief, he suddenly dies of what appears to be a heart attack.
Snake then contacts Meryl via codec, and agrees to meet her in the base's warhead disposal area on the condition that he contacts Metal Gear's designer, Dr. Hal "Otacon" Emmerich. As he emerges onto a canyon, Snake receives an anonymous codec call. The mysterious voice calls himself "Deepthroat" and warns Snake of a Tank ambush up ahead. Snake is confronted by Vulcan Raven in an M1 tank, but manages to defeat the two gunners and proceeds to the warhead disposal area. Snake locates Otacon in his lab. The ninja reappears, and Snake realizes that it is actually his former ally Gray Fox, whom he believed was killed years earlier. Otacon agrees to aid Snake remotely, using special camouflage to procure information and supplies while he remains invisible. Snake meets with Meryl and agrees for her to accompany him on his mission. Meryl gives Snake the PAL card Baker gave to her and as they head for the underground base, Meryl becomes possessed by Psycho Mantis's mind control tune and pulls her gun on Snake. Snake disarms Meryl and defeats Psycho Mantis who, before he dies, informs Snake that he read Meryl's mind, and discovered that he has "a large place" in her heart. After they reach the underground passageway, Sniper Wolf ambushes them, wounds Meryl, and after a brief duel captures Snake.
While Snake is imprisoned, Liquid confirms Snake's suspicion that they are twin brothers. Snake is then tortured by Ocelot and the player can choose whether or not to give in to the torture. When Snake is taken to his cell, he discovers the body of DARPA Chief Donald Anderson lying in the corner; however, though it was only hours before Snake watched Anderson die in front of him, the body has been decomposing as if he were dead for days. The body also appears to have been drained of its blood. Eventually Snake is able to escape by fooling the guard (by either lying in ketchup or hiding under a bed) or by waiting for the Ninja to come break him out.
As Snake makes his way up the facility's communications tower, he is ambushed by Liquid in an attack helicopter, but swiftly defeats him. As he emerges from the tower onto the snowfield he is confronted once again by Sniper Wolf. This time however, Snake defeats and kills Wolf in front of a grief stricken Otacon, who was infatuated with her. Nonetheless, Otacon continues to aid Snake.
Snake continues on to REX's hangar, while Vulcan Raven lies in wait. Raven, having shamanistic intuition, is able to discern Snake's heritage. He can also tell that Snake is a clone, saying that he is "from another world." Snake and Raven battle it out in a freezer warehouse, which results in Raven's death. During his death scene, Raven tells Snake that the man he saw die in front of his eyes was not the DARPA Chief but Decoy Octopus, a member of FOXHOUND. He also leaves Snake with a cryptic message of his violent future. His body is then completely devoured by ravens.
Infiltrating Metal Gear's hangar, Snake overhears Liquid and Ocelot preparing the launch sequence for Metal Gear REX. Thinking he is deactivating it by using the PAL card, Snake activates Metal Gear REX. Master Miller then reveals himself to be Liquid in disguise. He informs Snake that his entire mission was manipulated by the renegades to allow the launch of the nuclear weapon. Liquid explains that they are the product of the Les Enfants Terribles project, a government sponsored effort to clone Big Boss, that was conducted during the 1970s. Liquid explains that Snake received all of Big Boss' dominant genes, while he received all of the recessive genes. He also reveals to Snake the government's true reason for sending him in: the reprogrammed FoxDie virus would kill all the members of FOXHOUND, allowing the government to retrieve REX undamaged.
Liquid assumes control of Metal Gear REX and a battle ensues. Gray Fox suddenly appears and destroys REX's radome and dies trying to fend off the bipedal tank from Snake. Snake destroys Metal Gear REX and is challenged again by Liquid in person. He fights Liquid atop REX and defeats him after knocking him over the edge. He is then reunited with Meryl or Otacon, depending on the player's actions. They escape through an underground tunnel, while being chased by Liquid, in a jeep. After the two vehicles crash at the tunnel entrance, Liquid emerges and pulls a gun on Snake but suddenly dies from the FoxDie virus. Colonel Campbell, briefly ousted from command of the mission, calls off a nuclear air strike intended to obliterate the evidence of the day's events and officially declares Snake killed in action to stop the US government's search for him in the future.
After the end credits, the player finds out that Snake is the one with recessive genes whilst Liquid had the dominant genes. Solid Snake is revealed to have an indeterminate amount of time left before FoxDie kills him. Ocelot is revealed to be a double agent for the President of the United States. His intention was to obtain Baker's disk containing Metal Gear's specifications and deliver it to the President, and kill whoever knew of his true motives, one reason for his "accidental" killing of the DARPA Chief.
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