Years before the events of Uncharted: Drake's Fortune, Nate and Sam hunt for the treasure of infamous pirate Henry Avery, who plundered the equivalent of $400 million during the 1695 Gunsway heist. Alongside Rafe, the Drakes infiltrate a Panamanian jail to access the former cell of Avery's first mate, where Nate discovers a hollow St. Dismas cruciform.

Rafe impulsively murders the prison warden when he demands a cut, triggering a frantic escape which sees Sam shot by guards and Nate fleeing, believing his brother to be dead. Fifteen years later, Nate has retired with his wife Elena but misses the excitement of his old life. He is visited by Sam, who survived his injuries and has spent the intervening time incarcerated. He explains that he escaped with drug lord Hector Alcazar, who has demanded that Sam find Avery's treasure or be killed. Although reluctant to return to adventuring, Nate agrees to help Sam but tells Elena he has accepted a salvaging job.

Aided by Sully, the Drakes steal a duplicate Dismas cruciform from an illegal auction in Italy, bringing them into conflict with mercenary boss Nadine Ross and her employer, Rafe, who is still searching for Avery's treasure. A map inside the cruciform leads the Drakes to St. Dismas' cathedral in the Scottish Highlands. There, they discover a hidden temple wherein lies a map highlighting King's Bay in Madagascar.

In King's Bay, the Drakes and Sully learn that Avery, Thomas Tew, and ten other pirate captains pooled their treasures. Following clues to a tower in the city, Nate uncovers a map to Libertalia, a fabled pirate utopia founded by Avery and the other captains. The group returns to their hotel to find Elena waiting. Upset at Nate's deception and the appearance of his brother, whom Nate had never mentioned, Elena leaves. Nate refuses to abandon the quest and sends Sully after Elena.

The Drakes follow the map to an island and discover Libertalia. They find evidence of a civil war; the founders stole the city's treasure and moved it across the island to New Devon, an extravagant and well-fortified town built for them. En route, the brothers are cornered by Rafe, who reveals that he released Sam from jail two years earlier and that Sam's Alcazar story is a lie; Alcazar was killed in a shootout in Argentina six months prior. Deciding that he needs Sam, Rafe prepares to shoot Nate; Sam shields him, but Nate is knocked off a cliff and falls unconscious. Elena rescues Nate, who reveals his past: as teenagers, he and Sam discovered that their mother, a brilliant historian, had been researching Libertalia.

The boys decided to start new lives, changing their surname from Morgan to Drake to honor their mother's theory about Francis Drake's descendants. In New Devon, Nate and Elena learn that Libertalia descended into conflict over the treasure. Avery had Tew poison the other founders and they absconded with the hoard, but Tew betrayed Avery.

The group rescues Sam and convinces him to escape with them, but soon decides to pursue the treasure. Following Sam's trail, Nate finds Avery's treasure-laden ship, the Fancy in a cavern. Having already collected a large amount of treasure, Nadine refuses to risk more of Avery's traps, but Rafe coerces her by bribing her surviving men. Aboard the ship, Sam triggers a trap, trapping him beneath debris. Nate confronts Rafe and Nadine in the ship hold, where the skeletons of Avery and Tew lie, having killed each other over the treasure.

Nadine betrays Rafe and leaves him with Nate and Sam to die. Rafe challenges Nate to a sword fight, wanting to prove himself better. Nate drops a bundle of treasure on Rafe, killing him, and frees Sam. The pair return to Sully's plane, and the group escapes. Sam and Sully team up for a new job while Nate and Elena return home. Elena explains that Sam recovered gold and gave it to her. Realizing that they both need some adventure in their lives, she buys the salvage company for which Nate worked, installing Nate as the owner, and plans to revive her old exploration show. Years later, Nate and Elena have become successful salvagers.

After their teenage daughter Cassie (Kaitlyn Dever) discovers relics from their adventures, Nate decides to tell her their story.

Source: https://en.wikipedia.org/wiki/Uncharted_4:_A_Thief%27s_End