After working as a creative director at a public relations firm in Portland for several years, Cain began writing humor books in her spare time, including The Hippie Handbook: How to Tie-Dye a T-Shirt, Flash a Peace Sign, and Other Essential Skills for the Carefree Life (Chronicle Books, 2004), Confessions of a Teen Sleuth (Bloomsbury, 2005), and Does this Cape Make Me Look Fat? Pop-Psychology for Superheroes (Chronicle Books, 2006), which Cain co-wrote with her husband. Cain also composed a weekly column for Portland's alternative newspaper, The Portland Mercury and started contributing to Portland's major daily, The Oregonian in 2003. when she left marketing behind to focus on writing full-time. Her last column with The Oregonian was posted on December 28, 2008.
She wrote her first thriller Heartsick in 2004, while pregnant with her daughter. It was published on September 4, 2007, and was an instant New York Times bestseller. Sweetheart and Evil at Heart, the second and third in the series, respectively, are also New York Times bestsellers. Cain and her family currently reside in Portland, Oregon.