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.

Most of the game takes place fighting through the city, but there are also minor parts where a vehicle can be driven. Next to melee attacks (stomping, kicking, punching), a large number of weapons and explosives, there is a large focus on the abilities of the nanosuit, as implied by the game's promotional slogan "Be the Weapon". The suit has a limited amount of energy that needs to be recharged regularly. The suit's four modes of the original game have been brought back to two. Aside from the default Weapon mode, players can access Cloak and Armor as the two main modes. Cloak provides invisibility and suppresses sounds, while Armor strengthens protection. The suit can further be customized through many modules that provide specific abilities. Speed and Jump are still presented as additional abilities, but they are activated automatically when the player sprints or holds down the jump button respectively. These, along with many other modules, are called passive secondary powers because they drain energy when they are activated. In the other, secondary Tactical mode, items, buildings and enemies can be tagged through a tactical visor. This leaves the player in a vulnerable position with no weapon, but consumes no energy. A major difference to the first game is that multiple suit powers can be enabled at the same time. Other abilities are hit detection (shows the general direction of incoming bullets) and different weapon attachments.

The suit modes allow for different approaches to levels, based on brute force or stealth. A HUD shows a tactical radar with a basic map of the immediate terrain, nearby enemies, and a stealth meter that shows whether enemies are aware of your presence. Freedom of movement is more restricted than in the first game through the narrower city design, but there are many ways to progress through levels, and a larger focus on the verticality of the environment and using objects for cover and stealth, along with parkour-like movement that includes sliding and climbing up ledges.

The included multiplayer modes support up to twelve players simultaneously. The game modes are Instant Action (free for all), Team Instant Action (team-based death match), Crash Site (steal energy from alien pods), Assault (nanosuit operatives must download data from terminals defended by black ops soldiers), Capture the Relay, and Extraction (extract alien bio-ticks from defended locations).

The game supports stereoscopic 3D.