In 1979, Peña appeared in her first film, El Super, described as a "moving and melancholy comedy about a family of lower-middle-class Cuban refugees attempting to adjust to life in Spanish Harlem." She worked once again with director Leon Ichaso in his next feature, Crossover Dreams. She has appeared in films such as La Bamba, Down and Out in Beverly Hills, Jacob's Ladder, Lone Star, *batteries not included, Vibes and Rush Hour. In 2002, she starred in Showtime's Resurrection Blvd. as Tia Bibi Corrades in the episode "Justicia," which she also directed. In 2003, she appeared in and directed "It Was Fun While It Lasted," an episode of The Brothers Garcia.
Peña provided the voice of the character Mirage in Pixar's animated film The Incredibles. She guest starred in the 18th episode of season 2 of Numb3rs as Sonya Benavides, and in season 4 of Modern Family as Pilar, the Colombian mother of Gloria Pritchett. Although she spoke Spanish, she did not dub her own voice for Spanish releases. Peña was also noted for having starred in I Married Dora, a sitcom in 1987, as Dora Calderon, the title character. Writer-director John Sayles produced the critically acclaimed but short-lived television series Shannon's Deal (1989–1991), co-starring Peña. In 1996, Sayles wrote and directed the mystery film Lone Star and again cast her in a co-starring role.
Peña's first marriage, to William Kibler, ended in divorce in the early 1990s. She then married a carpenter, Hans Rolla, in 1994. They have two children together.
Peña died after a brief illness at the age of 55 on October 14, 2014, at Cedars-Sinai Medical Center in Los Angeles, California. Film reviewer Mario-Francisco Robles, Peña's nephew, confirmed her death in an article in Latino-Review the following day. The nature of her illness has not yet been disclosed.