Manfred contains supernatural elements, reflecting the popularity of ghost stories in England at the time. It is a typical example of a Romantic closet drama.

Friedrich Nietzsche was impressed by the poem's depiction of a super-human being and even wrote some music for it. Byron described this as a "metaphysical drama," written after his marriage failed amidst scandalous charges.

Attacked by the press and ostracized by society, Byron fled England for Switzerland in 1816 and never returned. Manfred was written immediately after this, and its main character is tortured by his own sense of guilt for an unmentionable offense, leading some critics to consider it autobiographical.

The unnamed but forbidden nature of Manfred's relationship to Astarte is believed to represent Byron's relationship with his half-sister Augusta. The supernatural references are clear throughout the poem. In one scene (Act III, Scene IV, Interior of the Tower), Manfred recalls traveling through time to Caesar's palace, "and fill'd up, As 't were anew, the gaps of centuries..."