She currently serves as co-host of Access Hollywood, a 30-minute entertainment news program produced and syndicated by NBC Universal Domestic Television Distribution. She has been with the show since its 1996 inception, and became co-host in 1999. O'Dell serves as a contributor for NBC's Today Show and Dateline NBC. In addition, O'Dell co-hosted the Miss USA and Miss Universe competitions in 2004 and 2005, respectively.

O'Dell has also appeared in several movies as either herself or a generic entertainment reporter, but has also taken on other acting roles. O'Dell was also the host and consulting producer of the USA Network talent competition Nashville Star over its first two seasons, but made the choice to leave the show upon its move from Saturday to Tuesday because of conflicts with her Access Hollywood schedule.

An accomplished journalist, O'Dell is the winner of three Associated Press Awards, two Society of Professional Journalists Awards and is a five-time Emmy Award nominee.

Nancy graduated from the now-defunct Coastal Academy High School in 1984. She went on to graduate Summa Cum Laude with a major in Marketing from Clemson University in South Carolina. During college she was a member of Kappa Kappa Gamma sorority. Then known as Nancy Humphries, she won the Miss South Carolina America pageant in 1987. In 1998, O'Dell was the youngest person ever elected to the South Carolina Music and Entertainment Hall of Fame. O'Dell is active in many national charities, including the American Red Cross, Best Buddies and March of Dimes.