The space shuttle is a reusable nuclear-powered spacecraft built before the Great War. There is one located in the ruins of San Francisco, though it lacks either rocket boosters or an external fuel tank; a quest involves finding fuel for it. The Enclave may have planned to use one or more shuttles to leave Earth and colonize other planets, but it seems likely that most were destroyed in the Great War or succumbed to neglect in the years that followed.
There are two endings for the Hubologists regarding the shuttle that are inaccessible due to incomplete scripting. If the Chosen One does not get them fuel, the Hubologists use a cheap alternative, resulting in the shuttle blowing up during liftoff. If they get fuel, the liftoff is without complications, but the shuttle's air insulation is damaged, resulting in the Hubologist crew suffocating in space.
A space shuttle appears only in Fallout 2.