Even though Uncharted 4: A Thief’s End adds Nathan Drake’s brother Sam, you won’t be able to play as him or any other character from the single player campaign.
In The Last of Us, Naughty Dog allowed players to control both Joel and Ellie in different parts of the game. Even though Joel is the “main” character, there was a significant portion of the game that put you in the shoes of Ellie.
German publication PlayM had the opportunity to preview Uncharted 4: A Thief’s end recently. Naughty Dog notified them that the game won’t have any other playable characters. They said much like the other games, it has always been about Nathan Drake. The focus for the new game is still Nathan Drake being the only character that gamers control.
However, that’s not to say Nathan Drake will always be alone in his adventure. As seen in the E3 gameplay footage, Sam Drake still plays a huge part in the game. He is also an interesting character because Nathan thought that his brother died years ago. Now he’s back and needs help from Nathan.
Not a lot has been revealed about Uncharted 4: A Thief’s End’s multiplayer mode, but it’s possible you can be other playable characters in that mode instead.