The hero of Shadow Moses, Solid Snake is the last surviving "Son of Big Boss". Following the Manhattan Incident, Snake went into hiding with Otacon and Sunny, Olga's daughter. However, with the conscience of his brother, Liquid, now apparently back and close to world domination, Snake, now suffering severely advanced ageing as a result of the cloning process, is called out of retirement by Colonel Campbell with one mission: to assassinate Liquid. Thus, the player assumes control of Snake as the main protagonist of this game.
The sister of Gray Fox, the FOXHOUND agent who died by Solid Snake's hand, Naomi was one of Snake's supporting crew during the Shadow Moses incident. During the incident, she injected him with the FOXDIE virus as vengeance for her brother's death, believing full well that programming it to kill Liquid would also kill him. Her plan failed due to Snake's unexpected genetic differences from Liquid, and she was imprisoned. Later broken out by Ocelot, she is being held prisoner by him, forced to work on his plans.
Meryl is the Colonel's daughter: the result of an affair between Campbell and his brother's wife. In order to follow in her "uncle's" footsteps, she joined FOXHOUND before the Shadow Moses incident. She was imprisoned when she refused to take part in the rebellion, only to be rescued later by Solid Snake. Despite having feelings for her rescuer, Snake abandoned her not long after. She is now the commander of a reformed FOXHOUND squad named Rat Patrol 01 .
A former Genome soldier, Johnny Sasaki somehow escaped imprisonment after the Shadow Moses incident. He made a brief appearance during the Big Shell incident, though was still not much use due to his severe diarrhoea. He is now a member of Rat Patrol, serving under Meryl, for whom he still has a secret infatuation.
Jonathan is one of the members of Rat Patrol. His hair is shaved in such a way, that when viewed from behind it appears as an exclamation point. Easy going by nature, he can fall asleep anywhere, even in the middle of a battlefield. According to Meryl, he is wary of people sneaking up on him, as she warned Snake not to approach him from behind.
After losing his hand during the Shadow Moses incident, Revolver Ocelot had his right arm replaced with Liquid's. Liquid's consciousness periodically took control of his body, disrupting his plans heavily during the Big Shell incident. Now, Liquid's mind had taken full control of Ocelot's body, and the two have merged into one being: Liquid Ocelot.
Vamp is the last surviving member of Dead Cell, the terrorist group that took control of the Big Shell in 2009. Now, he serves under Liquid Ocelot's leadership and still holds a personal vendetta against Raiden. Despite dying by Raiden and Snake's hands almost a dozen times, his nanomachines grant him the gift of rapid cell regeneration, healing his wounds at an accelerated rate and rendering him immortal. He also possesses several other bizarre, superhuman abilities, as well as a taste for human blood. Vamp is also bisexual.
Colonel Roy Campbell was Snake's commanding officer during his time at FOXHOUND and during the Shadow Moses Island. An AI based on him assisted Raiden during the Big Shell incident. Now holding a position at the UN's security council, he recently discovered information on the location of Liquid Ocelot, and dispatches Snake on his mission as a personal favour.
During the Big Shell incident, Raiden infiltrated the facility, believing he was under orders from FOXHOUND to neutralize the terrorist threat. In reality, he was a pawn in the Patriots' master plan, his entire mission scripted as an exercise to provide test data for GW. He supposedly destroyed GW with the help of Snake, and decided to start his life over again with his fiancée, Rose, and the child they were expecting. However, following Rose's apparent miscarriage, Raiden left to travel the world, only to be kidnapped by the Patriots and used as a test subject for their new Cyborg Ninja program. He did, however, escape with the help of the Paradise Lost army and rescued Sunny Gurlukovich from them also.
Dr. Hal Emmerich Ph.D was one of the main scientists working on Metal Gear REX during the Shadow Moses incident, before being rescued by Snake after discovering that he was building a nuclear weapon. His shock at finding this out was worsened by his family's dark history with nuclear weapons. Determined to help mankind, he and Snake created the anti-Metal Gear NGO, Philanthropy, but the organisation was branded a terrorist group after the events of the Manhattan incident. Nevertheless, he remains in hiding with Snake and Sunny Gurlukovich. He holds a personal vendetta against Vamp for the murder of his sister, Emma, who, prior to the Big Shell incident, he had not seen in years.
Big Mama is the leader of the Paradise Lost army. During Operation Snake Eater, she, under the name EVA, assisted Naked Snake in his mission to assassinate The Boss, only to end up falling in love with him.