A Thief's End
Several year prior to the events of Drake's Fortune, Nate 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, but an expedition by Drake's supposed descendant, Nathan Drake, and reporter 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 latest discovery.