Within The Resistance, several pieces stand out that encapsulate the album's ambition. The suite "Exogenesis", divided into three parts and lasting 13 minutes, tells a story about the end of humanity and the search for a new beginning in space, featuring the participation of an orchestra of over 40 musicians. The first single, Uprising, drew on the influence of bands like Goldfrapp and the glam rock of the 70s and 80s. On the other hand, Undisclosed Desires, with a sound influenced by contemporary R&B and David Bowie's song Ashes to Ashes, marked a milestone as Muse's first song without guitar or piano. Another notable track is I Belong to You, where Chris Wolstenholme used an acoustic bass treated with an Akai Deep Impact bass synthesizer, and which also incorporates a fragment of French opera.
The release of The Resistance on September 14, 2009, was met with mostly positive reviews, which praised its concept, instrumentation, and vocal influences, although some considered it excessive. Despite this, the album reached number one in 19 countries and became one of Muse's most successful works, selling over five million copies worldwide and winning the Grammy Award for Best Rock Album at the 53rd Annual Grammy Awards. The band promoted the album with a tour that included 30 concerts.