Drake's Deception is the third main game in the Uncharted series. A couple of years have passed for Nathan Drake, an Indiana Jones-like adventurer with a knack to find himself in all kinds of trouble. As usual, he always pulls his loyal friend and companion Sully along with him. The story takes the player back to Nathan's youth and how he met Sully when they were both after a ring and then returns to modern times. The game immediately introduces a whole new gameplay element that focuses on melee combat that consists of kicking and evading enemy hits, and a combination of both which may result in certain special moves during which Nate can also interact with surrounding objects for finishers. Quick time events are also used in melee combat to break free or to evade incoming attacks.

The story eventually builds up to a search for the legendary lost city Iram which takes the player through various different locations and environments, from the dark streets of England to a hidden castle in France, a monastery in Syria, and Rub' al Khali, one of the largest deserts in the world. Gameplay is very similar to the previous two games, with many contextual moves and the newly added melee art of fighting while not carrying a weapon. A large part is still spent climbing, using acrobatic movement, and shooting opponents with two types of weapons that can be exchanged with those of dead enemies. The cinematics are much more seamless with the actual gameplay. There is also a slight focus on stealth now, encouraging the player to use cover and stealth skills to avoid large battles. True to the series, there are many optional artifacts lying around to collect during the adventure, which results in trophy awards. At certain moments larger puzzles need to be solved by manipulating items in the environment and consulting clues in Drake's notebook. When the player gets stuck for too long, hints are shown gradually and automatically.

Aside from the story campaign which is split into 22 chapters, the game comes with cooperative and competitive multiplayer modes.