Two years on from the first game, treasure hunter Nathan Drake is approached by an old associate, Harry Flynn, and Flynn's girlfriend Chloe Frazer with a job: steal a Mongolian oil lamp tied to Marco Polo's doomed 1292 voyage home from China. The plan is to cheat Flynn's client and keep Polo's treasure for themselves — though, unknown to Flynn, Chloe and Nate have a history, and Chloe intends to blackmail Flynn and slip away with Nate and whatever they find.
Nate and Flynn break into an Istanbul museum and recover the lamp, which hides a map and a flammable resin revealing that Polo's fleet was wrecked in Borneo while carrying the Cintamani Stone from the fabled city of Shambhala. Flynn promptly double-crosses Nate, leaving him to be arrested.
Three months later, Chloe springs Nate from jail alongside his longtime friend Victor Sullivan, revealing that Flynn now works for Zoran Lazarević, a Serbian war criminal hunting the same stone. In Borneo, Nate and Sully infiltrate Lazarević's camp with Chloe planted as a mole. Nate deduces that the stone never actually left Shambhala and uncovers a temple holding the bodies of Polo's crew, along with a phurba dagger and a map showing that whoever carries it can reach Shambhala through a temple in Nepal. Cornered by Flynn and his men, Nate and Sully barely escape.