Touring with the likes of Marilyn Manson and Korn, as well as a stint on Ozzfest, expanded their fan base and led up to Powerman 5000's 1997 science fiction-esque follow-up, Tonight the Stars Revolt! During shows and promos for the album, the band was often found sporting spacesuits and other sci-fi paraphernalia. The record went platinum, helped in part by the success of singles "When Worlds Collide" and "Nobody's Real" on MTV. The halted release of a since aborted album entitled Anyone for Doomsday? signaled the departure of longtime bassist Dorian Heartsong (aka Dorian 27) and drummer Al Pahanish (aka Al 3) in early November of 2001. A year later, drummer Adrian Ost (aka Ad7) was added to the group; bassist Siggy Sjursen joined 40 auditions later before 2002 came to a close.

Powerman 5000, including Spider and longtime guitarists Adam Williams (aka Adam 12) and Mike Tempesta (aka M.33), was then back in full effect. Transform, their fourth album, marked the band's new more punk-inspired, less industrial sound and new lineup when it was released in spring 2003. It debuted at number 25 on the Billboard charts and produced a hit in the song "Free," though Dreamworks dissolved in the middle of the album's promotion. A rarities collection appeared in 2004 on Spider's own Megatronic label; more lineup changes would occur before the eventual release of the band's fifth full-length. Williams and Tempesta exited to be replaced on guitar by Johnny Heatley and ex-Alien Ant Farm's Terry Corso. Powerman 5000 inked a deal with DRT Entertainment in spring 2006, and Destroy What You Enjoy surfaced that August. Subsequent tour dates through fall were played.