Vassey played Emily Ann Sago on the soap opera All My Children from 1988 to 1991. From 2004 to 2005 she had a recurring role on the series Tru Calling as Dr. Carrie Allen. She appeared on the Two and a Half Men episode "The Last Thing You Want to Do Is Wind Up with a Hump" (2003).

Since 2005, Vassey has had a recurring role as Wendy Simms on CSI: Crime Scene Investigation. Starting with the tenth season, Vassey was promoted to a regular cast member and began appearing in the show's opening credits. Entertainment Weekly reported on June 1, 2010 that Vassey will not be returning for the show's eleventh season.

Vassey has a cameo on Joss Whedon's web-based musical, Dr. Horrible's Sing-Along Blog, as "Fury Leika".

Along with fellow actress Kristin Bauer, Vassey runs a company called Neurosis to a T(ee), which designs and sells slogan-covered t-shirts for women. The slogans poke fun at female worries and neuroses, often relating to relationships.