Two years after the events of the Shadow Moses Incident, Solid Snake and Otacon, working as Philanthropy, receive intelligence about a new type of Metal Gear being transported through the Hudson River. As Snake boards the tanker, it is seized by Russian mercenaries led by Revolver Ocelot, who intend to steal the weapon.

In 2009, the player takes control of Raiden, a rookie agent under the Colonel, apparently a member of a reformed Foxhound unit. His first assignment is to infiltrate the offshore clean-up facility Big Shell and rescue the President of the United States of America, who has been kidnapped by the terrorist organization Sons of Liberty.

As the mission continues, Raiden finds that almost everyone he speaks with seems to be hiding something, and it becomes difficult to tell friend from foe.