Former special operative MacGruber is called back into action to take down his arch-enemy, Dieter Von Cunth, who's in possession of a nuclear warhead and bent on destroying Washington, D.C.

In an age when Machines dominate the world, the fate of man rests in the hands of an outlaw and an android.

In the Dzhugdzhur Mountains, Eastern Siberia, the criminal Dieter Von Cunth steals a Russian X5 nuclear warhead. Colonel James Faith travels to Rio Bamba, Ecuador, with the efficient Lieutenant Dixon Piper to summon the retired special operative MacGruber to retrieve the X5. MacGruber is considered deceased after the death of his beloved wife Casey by his archenemy Cunth in their wedding. MacGruber teams up with Piper and Vicki St. Elmo and they learn that the evil Cunth intends to use the warhead to destroy Washington D.C.