Although most of the gameplay reflects a distinctly fantasy genre, the overarching plot of the first nine games has something of a science fiction background. The series is set in a fictional galaxy as part of an alternative universe, where planets are overseen by a powerful race of space travelers known as Ancients. In each of the games, a party of characters fights monsters and completes quests on one of these planets, until they eventually become involved in the affairs of the Ancients. Might and Magic could as such be considered an example of science fantasy.

Van Caneghem has stated in interview[8] that the Might and Magic setting is inspired by his love for both science fiction and fantasy. He cites The Twilight Zone and the Star Trek episode For the World is Hollow and I Have Touched the Sky as having inspired Might and Magic lore.

The first five games in the series concern the renegade guardian of the planet Terra, named Sheltem, who becomes irrevocably corrupted, developing a penchant for throwing planets into their suns. Sheltem establishes himself on a series of flat worlds known as nacelles (which are implied to be giant spaceships) and Corak, a second guardian and creation of the Ancients, with the assistance of the player characters, pursues him across the Void. Eventually both Corak and Sheltem are destroyed in a climactic battle on the nacelle of Xeen.

The sixth, seventh and eighth games take place on Enroth, a single planet partially ruled by the Ironfist dynasty, and chronicle the events and aftermath of an invasion by the Kreegan (colloquially referred to as Devils), the demonlike arch-enemies of the Ancients. It is also revealed that the destruction wrought by the Ancients' wars with the Kreegan is the reason why the worlds of Might & Magic exist as medieval fantasy settings despite once being seeded with futuristic technology – the worlds have been 'cut off' from the Ancients and descended into barbarism. The first through third games in the Heroes of Might and Magic series traces the fortunes of the Ironfists in more detail. None of the science fiction elements appear in the Heroes series besides the appearance of Kreegan characters in Heroes of Might and Magic III and IV.

The Ubisoft release Might & Magic X: Legacy departs from this continuity and is set in the world of Ashan.[9] Ashan is a high fantasy setting with no science fiction elements in its lore