In 2004 Dewan made her Acting debut on the Fox Sitcom television series Quintuplets. Dewan has since guest appeared on shows such as The Young and the Restless, Joey and Melrose Place.
In 2005 Dewan portrayed the role of the protagonist in the independent low-budget Supernatural Horror film Tamara. The film centers on an outcast student who dies in a prank gone wrong and returns from the dead to get her revenge. The film was an initial financial and critical failure. In 2006 Dewan made notable appearances in films The Grudge 2 and Take the Lead. That same year Dewan starred as the female lead in the Dance Drama film Step Upas Nora Clark a dance student whom is partnered with a troubled Tyler Gage who is sent to spend his community service as a janitor at the school. The film opened to widespread success and went on to make $119 million worldwide. The role is widely considered Dewan’s breakout role.
In August 2008 Dewan starred in the Lifetime Made-for-Television film Fab Five: The Texas Cheerleader Scandalwhich follows five teenagers notorious for breaking the rules. Dewan portrayed the role of Coach Emma Carr who looks to discipline these five young girls. In November 2009 Dewan appeared in the Straight-to-DVD Comedy filmAmerican Virgin alongside Rob Schneider.
In August 2010 it was announced Dewan was cast in the ensemble Crime Heist film Setup. Dewan was to star alongside 50 Cent, Bruce Willis and Ryan Phillippe. Production began in November 2010 in Grand Rapids, Michigan and follows a group of friends who are involved in a potentially deadly diamond heist. The film was to be released theatrically in July 2011 but the film was pushed back. The film eventually was released Straight-to-DVD on the 20 of September 2011 to mixed reviews.
Along with friends Reid Carolin, Adam Martingano, Brett Rodriguez and husband Channing Tatum, Dewan started a production company called 33andOut Productions.Their first production is a documentary called Earth Made of Glass that follows the Rwandan President Paul Kagame and genocide survivor Jean-Pierre Sagahutu. The film was selected to premiere at the 2010 Tribeca Film Festival.
In March 2011 Dewan was announced to have been cast in the NBC pilot The Playboy Club. In May 2011 NBC picked up the series for a full season order. Dewan portrayed the role of Bunny Janie a very provocative playboy bunny who works at a Playboy Club in Chicago during 1961 and was confirmed to be a series regular on the series. The series premiered on September 19 2011 to a 5.2 million viewers and mixed reviews from critics. Due to low ratings NBC cancelled the series after just three episodes in October 2011.
In September 2010 Dewan was announced to appear in the Romantic Comedy film Ten Year. The film is produced by Husband Channing Tatum. Filming took place in January and February 2011 in New York, California and New Mexico. The film is to be released in September 2012.