A Thief's End
Several year prior to the events of Drake's Fortune, Nathan Drake and his brother Samuel Drake, along with Rafe Adler, went to Panamá to collect the Saint Dismas Cross in the Panamanian jail led by the prison's corrupted warden Vargas. Though successful, Sam was wounded and ended up staying in the prison for years. Nate abandoned the expedition, and Rafe continued searching for decades.
It was off the coast of Panamá that for centuries, Francis Drake was believed to have been buried at sea. In Drake's Fortune, an expedition by Nathan Drake and Elena Fisher revealed that the coffin was empty, except for Drake's lost diary. This proved Nate's theory that Drake had faked his death to cover up his discovery of El Dorado.
The two were soon ambushed by a gang of pirates led by Eddy Raja. After a lengthy firefight, their salvage vessel became extremely damaged and was eventually blown to pieces. They managed to jump overboard before being caught in the explosion, and were rescued by Victor Sullivan. The three of them flew back to shore in Sullivan's seaplane. Back at shore, Nate and Sully discussed Sir Francis' journey to find El Dorado, while Elena was preoccupied with a phone call with her producer. The two decided that if they were to go after the treasure, it would benefit them if they left Elena behind, despite how well she can hold her own. The two sailed off without Elena, who tried to give chase but was not fast enough.
Panamá in Drake's Fortune
Initially, all that was seen of Panamá in Drake's Fortune, was a large, plain sea, where Nate and Elena fished out Francis Drake's coffin. When Sully flew them back to the shore, what was seen is a small, tropical beach area, featuring cottage-like houses surrounded by lush environment. Here lies a dock, with Sully's boat, Sullivan's Travels, initially docked beside it. This island is the only specific location in the game that is not playable in gameplay.