Several years before the events of the first game, Nate and Sam hunt for the treasure of pirate Henry Avery, who plundered a fortune during the 1695 Gunsway heist. Alongside Rafe, the Drake brothers infiltrate a Panamanian jail to access the former cell of Avery's first mate, where Nate discovers a hollow St. Dismas idol. When the prison warden who aided them demands a cut, Rafe impulsively kills him, triggering a frantic escape. Nate and Rafe successfully escape, but Sam is shot by guards and presumed dead. Fifteen years later, following the events of the previous game, Nate has retired in New Orleans with his wife Elena but misses the excitement of his old life. He is visited by Sam, who survived the gunshots and has spent the intervening time incarcerated. He explains that he escaped with drug lord Hector Alcazar, who demands that Sam find Avery's treasure or be killed. Nate agrees to help Sam, lying to Elena that he has accepted a salvaging job in Malaysia which he had refused.
Players traverse several environments, moving through locations including towns, buildings, and wilderness to advance through the game's story. Players use firearms, melee combat, and stealth to combat hostile enemies. For most of the game, players control Nathan Drake—a treasure hunter who is physically adept and can jump, sprint, climb, swim, scale narrow ledges and walls, swing with a rope, use a grappling hook and perform other acrobatic actions. Players also drive vehicles during some gameplay segments.
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