Resistance 2 is te sequel to First Person Shooter Resistance: Fall of Man.

A Black Ops aircraft takes Sgt. Nathan Hale to the base of the Special Projects Research Administration (SPRA) in Iceland. Hale arrives at the base and discovers that there are others like him that are resistant to the Chimera virus who have been collected together from around the world by the SPRA. The result is a task force called 'The Sentinels'. The base then comes under attack by Chimera forces and 'The Sentinels' manage to escape to the United States. Two years after the Chimeran defeat in Great Britain, the Chimera launch a full-scale aerial invasion on both the east and west coasts of the United States.

The game will feature two campaigns. A single player campaign which will follow the story of Nathan Hale and a co-operative campaign that will have a storyline running parallel to Hale's campaign. The co-operative campaign will support up to 8 players online or 2 player split screen with classes including a medic class, a heavy weapons class, and a special ops class. The online multiplayer aspect of the game will support up to 60 players online. The game will also feature 12 new Chimeran enemies.