Crysis 2 is the sequel to Crysis and it is the second main game in the series, following the original title and the stand-alone expansion Crysis: Warhead. It is a first-person shooter where the basic weaponry is enhanced with a nanosuit that provides additional abilities, as featured in the first game. Many basic elements from its predecessor are borrowed, with the change of scenery as a notable difference; the game moves away from the jungle environment on a tropical island, as featured in Crytek's earlier title Far Cry as well, to a darker urban warfare scenery set in the destroyed cityscape of a future New York City in 2023, three years after the events of the first game.

The player assumes the role of Alcatraz, a force recon marine and a different protagonist than in the first game. New York City is ravaged and partially under martial law after an outbreak of the Manhattan virus that causes cellular breakdown. At the same time the city is struck by an infestation of the alien race Ceph, which was also present in the original game. Alcatraz is initially deployed as a regular marine as a part of C.E.L.L., a private military organization part of Crynet who developed the nanosuit. During the course of an early mission Alcatraz ends up by himself and meets the infected major Laurence Barnes who owns an updated 2.0 version of the suit. He passes it on to Alcatraz who consequently has to take on the Ceph as well as fight off C.E.L.L. soldiers, who assume he is Barnes because of the suit. Crynet hunts Barnes because he is an active biohazard through the infection and has stated criticism of the side effects that come along with wearing the suit.