Cain was born February 5, 1972 in Iowa City, Iowa, to Mary Cain and Larry Schmidt. Cain spent her early childhood on a hippie commune outside of Iowa City. Her father resisted the Vietnam draft and her parents lived "underground" for several years. In 1978, she moved with her mother to Bellingham, Washington, where she attended Lowell Elementary School, Fairhaven Middle School, and Sehome High School. She spent the school year in Bellingham with her mother and the summers in Florida with her father and stepmother and stepbrother.
Cain left Bellingham after high school to study political science at the University of California, Irvine, where she wrote for the New University newspaper and became the opinion editor. After graduating in 1994, she attended the graduate school of journalism at the University of Iowa.
While at Iowa, she wrote a weekly column for The Daily Iowan. Her master's thesis at the University of Iowa became Dharma Girl, a memoir about Cain's early childhood on the hippie commune. One of her professors presented it to several editors for review, and Seal Press picked it up as Cain's first published work. She was 24 years old.
She traveled across the United States on book tour with Dharma Girl, living for a brief period in Portland, Oregon and then in New York City. After a year in New York, she returned to Portland, and edited an anthology for Seal Press titled Wild Child: Girlhoods in the Counterculture.
Cain is married to Marc Mohan, a video store owner and film reviewer for The Oregonian. They have one daughter, Eliza.
Cain and her family currently reside in Portland, Oregon.
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.
In March 2016, Cain started writing a new Marvel Comics series, Mockingbird, the first solo series about the character. The series ran for eight issues. As reported in various media, harassment by individuals opposed to the title's feminist themes led Cain to quit the social network Twitter, but Cain herself wrote that she left Twitter because of the site's "ordinary daily abuse" rather than specific harassment. She has since returned to Twitter.Named 6th best book of the year (2008) by Stephen King in Entertainment Weekly for Heartsick and Sweetheart
Amazon Mystery/Thriller of 2007 for Heartsick
Named one of Four Hot Authors for Fall 2007 by Entertainment Weekly
Heartsick optioned as a film in September 2007
Booksense 76 Pick for Heartsick
Barnes & Noble Developing Writer pick for Heartsick
New York Times Book Review editor's choice for Heartsick and Confessions of a Teen Sleuth: A Parody