The third release in GSC Game World's post apocalyptic first-person shooter series, S.T.A.L.K.E.R.: Call of Pripyat once again finds gamers in a fictional version of the Chernobyl Zone of Alienation, where a second nuclear disaster dramatically altered the local environment. When a large-scale airborne mapping operation designed to survey the "Zone" results in a number of helicopter crashes, the Ukrainian government sends in their special agent to determine what happened.

As this agent, players move freely throughout a realistic re-creation of the town of Pripyat and its surrounding geography, collecting artifacts, trading with fellow explorers, and battling radiation, anomalies, and mutated monsters. The main goal is to investigate the helicopter crash sites and locate any survivors, but numerous side missions become available as gamers come into contact with various factions located within the Zone. Call of Pripyat makes use of a number of RPG-style elements, such as weapon damage and upgrades, and once players finish the primary quest they have an option to remain in the Zone to continue exploring and finish side missions.