In 2001, Manning had a high-profile role in the teen romance "crazy/beautiful", stealing scenes from talented co-stars Kirsten Dunst and Jay Hernandez with her energetic and charming performance as a party girl. One of the few highlights of the film (which was driven by an uninspired middle-of-the-road soundtrack) was Manning's moment in the sun, ditching school and singing the appropriate "Bein' Bad", a song co-written by the actress and her brother.

Much of Manning's career has revolved around music, from a cameo as a groupie in the 1999 ABC movie "Come On, Get Happy: The Partridge Family Story" to supporting roles opposite Britney Spears and Eminem in their feature debuts (2002's "Crossroads" and "8 Mile", respectively). 2002 also saw the actress take on a role alongside such luminaries as Michelle Pfeiffer, Robin Wright Penn and Renee Zellweger in "White Oleander," Peter Kominsky's feature adaptation of Janet Fitch's bestseller.

Manning was center stage, alongside co-star Vincent Kartheiser, in the indie drama "Dandelion" (2004), as a pair of star-crossed small town lovers. Along with supporting roles in the minor films "Lucky 13" (2004) and "Debating Robert Lee" (2004), Manning had notable appearances in A-list productions as well: she appeared briefly in Anthony Minghella's acclaimed Civil War melodrama "Cold Mountain" (2003) as part of a family of would-be seductresses, and had an amusing reappearing role in the Ashton Kutcher, Amanda Peet romantic comedy "A Lot Life Love" (2005) as Kutcher's annoying sister who makes the most out of the line "You're a dick, Oliver." In “Hustle & Flow” (2005), she delivered her most appealing performance yet when she played a tough-as-nails hooker whose pimp (Terrance Howard) decides to become a rap star. The movie won the Audience Award for Best Dramatic Feature at the 2005 Sundance Film Festival and emerged with enough buzz to make one swoon.