Rubin-Vega is the youngest of three children. Her father, a carpenter, died when she was two and the following year she was sent to Washington, DC to live with an aunt. At age nine, she reunited with her mother and two older brothers in Manhattan's Greenwich Village. After her mom died in 1979, Rubin-Vega began to rebel and her stepfather eventually kicked her out of the house. The teenager began tagging along with friends to recording sessions and eventually landed a few gigs as a studio singer. By the late 1980s, she was writing her own songs and leading the all-girl group Pajama Party.
While performing in musical theater was never a priority for her, Rubin-Vega was persuaded by her agent to audition for a 1994 workshop of a new stage musical with a contemporary pop score, "Rent". Immediately impressing Larson, Rubin-Vega was offered the lead role of Mimi, the S&M dancer with AIDS. Following that workshop, she segued to Randy Newman's "Faust" at the La Jolla Playhouse and then returned to NYC to recreate Mimi in the Off-Broadway staging of "Rent". Fueled partly by the untimely death of Larson, the show quickly sold out and moved to Broadway where it became a cultural phenomenon. Rubin-Vega remained with the show for about a year before departing to try her hand at other ventures.
Although she had made her film debut in a small role in the indie "I Like It Like That" (1994), Rubin-Vega had her first major movie role as a detective investigating charges of rape in the erotic thriller "Wild Things" (1997). Her somewhat amateurish performance marred what was destined to become a camp classic thanks to its cheesy plot. She fared better as a dancer with genuine feelings for Robert De Niro in Joel Schumacher's "Flawless" (1999). Rubin-Vega also returned to the stage to act in the dramatic pieces "Gum" and "Two Sisters and a Piano" before returning to musicals as Magenta in the Broadway revival of "The Rocky Horror Show" in fall 2000.