Lyrically, the song explores the collapse of industrial civilization. Lead singer Matt Bellamy describes a terrifying scenario where humanity loses its "supremacy" over the planet.

Musically, "Supremacy" is defined by its massive seven-string guitar riff and orchestral hysteria, often compared to the syncopated style of Led Zeppelin’s "Kashmir". Drummer Dom Howard famously noted the song's "Bond vibe," Likening its middle section to Paul McCartney’s "Live and Let Die". While the band half-jokingly suggested it for the 2012 film Skyfall , Adele’s theme was ultimately chosen. This "spy-movie" aesthetic remains central to the song's identity, providing a cinematic backdrop for its heavy themes.

The official video for "Supremacy" by Muse is a surreal juxtaposition of bombastic, James Bond-inspired rock and unexpected "beach goth" imagery. Directed by Terry Hall and released in early 2013, the video serves as a visceral companion to the opening track of the band's sixth studio album, The 2nd Law .