Duke Nukem: Total Meltdown contains all three original episodes of Duke Nukem 3D. In addition, it includes a new episode called Plug n' Pray. This episode contains six levels and one secret level. There are also new enemies in this level, ranging from new types of Pig Cops to a new boss named CyberKeef.
Duke Nukem: Total Meltdown features remixed, original, and rearranged PC music.
Set on Earth in the 21th century, the game takes place right after Duke Nukem II. When Duke returns to Earth, his space cruiser is shot down over Los Angeles. It is then that Duke learns of an ongoing alien invasion and that the aliens have mutated the LAPD into Pig Cops. Duke then vows to to stop the invasion.