Uncharted 2 is an action-adventure game played from a third-person perspective, with the player in control of Nathan Drake. Drake is physically adept and is able to jump, climb, and scale narrow ledges and wall-faces to get between points. Drake can be equipped with up to two firearms – one single-handed and one two-handed – and a limited supply of grenades. Drake can pick up weapons, automatically replacing the existing weapon he was using, and additional ammunition from killed foes. The player can direct Drake to take cover behind corners or low walls using either aimed or blind-fire to kill his enemies. The player can also have Drake fire while moving. If Drake is undetected by his enemies, the player can attempt to use stealth to take them out, such as by sneaking up behind them to knock them out with one hit, or by pulling an unsuspecting foe over a ledge from which Drake is hanging.^[7] Some areas of the game require the player to solve puzzles with the use of Drake's journal, which provides clues towards the puzzles' solutions. When enabled, a hint system provides gameplay clues, such as the direction of the next objective.

Throughout the game are special treasures that may be hidden or in difficult-to-reach places that the player can collect. Collecting these treasures, along with completing certain feats within the game, is tracked by the awarding of medals, which gives the player in-game money to use to unlock extra content on the disc, including concept art, game movies, and game cheats such as guns with infinite ammunition. The statistics tracked for a large portion of the in-game medals are used to award PlayStation 3 trophies