Metal Gear Solid 4 is set in 2014, five years after the Big Shell incident and nine years after the Shadow Moses incident. The world economy relies on continuous war, fought by PMCs, which outnumber government military forces. PMC soldiers are outfitted with nanomachines to enhance their abilities and control the stress of the battlefield. The control network created through these nanomachines is called Sons of the Patriots (SOP), and Liquid Ocelot is preparing to hijack the system. Snake accepts a request from Roy Campbell to terminate Liquid, with Otacon and Sunny providing mission support from the Nomad aircraft.

Metal Gear Solid 4: Guns of the Patriots is the final chapter in the saga of Solid Snake which sends him around the world in pursuit of his arch nemesis, Liquid Ocelot. Armed with new gadgets and abilities, Solid Snake must shift the tides of war into his favor, using the chaos of the battlefield to infiltrate deep into enemy territory. In his globetrotting final mission, Snake must sneak deep into enemy locations in the Middle East, South America, and other corners of the earth to foil Liquid Ocelot's plans for total world domination.