Moss then parted ways with So So Def in favor of its parent label, Columbia Records, to release his third album, Unleashed (2003). It peaked at number three on the Billboard 200 and was his first release after dropping "Lil'" from his stage name. His fourth album, Wanted (2005), spawned the singles "Let Me Hold You" (featuring Omarion) and "Like You" (featuring Ciara), which peaked at numbers four and three on the Billboard Hot 100, respectively, becoming his highest-charting songs. His 2006 single, "Shortie Like Mine" (featuring Chris Brown and Johntá Austin), peaked within the chart's top ten and preceded the release of his fifth album, The Price of Fame (2006). His sixth album, New Jack City II (2009), was met with trailing critical and commercial response, serving as his final album on a major label. He briefly signed with Birdman's Cash Money Records in 2009 to release a series of promotional singles—including "Ain't Thinkin' 'Bout You" (featuring Chris Brown) and "Sweat" (featuring Lil Wayne)—leading up to his seventh album Underrated, which remains unreleased. He then signed with Puff Daddy's Bad Boy Records in 2015, and likewise released no albums with the label.

Moss first appeared in the 2002 film All About the Benjamins as a cameo. That same year, Moss was cast in the lead role for the sports comedy film, Like Mike. He later starred in the films Johnson Family Vacation in 2004 and Roll Bounce in 2005. He played a supporting role in the film The Fast and the Furious: Tokyo Drift in 2006, a character he reprised in F9 (2021). Moss appeared in five episodes of the television series Entourage, and starred as Brody Nelson in CSI: Cyber until the show's 2016 cancellation.