Russo was born in Burbank, California, the daughter of Shirley (née Balocca), a factory worker and barmaid, and Nino Russo, a sculptor and car mechanic who left the family when Rene was two. Her father was of Italian descent, and her mother's ancestry was half Italian and half German and English. Russo grew up with her sister, Toni, and their single mother. She attended Burroughs High School (where her classmates included director Ron Howard), but eventually dropped out in the tenth grade. To help her family, she began taking a variety of part-time jobs including working in an eyeglass factory, and as a movie cashier.