In Van Buren, players would start as a prisoner, with their backstory determined during character creation. The game would begin with an attack on the prison, allowing the player to escape into the wasteland and influence the fate of various factions.

The storyline of Van Buren revolved around an ongoing war between the Brotherhood of Steel and the New California Republic, with player choices impacting the conflict and the world around them. The ultimate plot involved a rogue scientist's plan to launch nuclear missiles, with the player's decisions determining their targets.

Van Buren stands out with its intricate faction dynamics and the potential for player-driven outcomes, elements that would later influence the narrative of Fallout: New Vegas.