Keena portrayed Bertha in a stage reading of Strindberg's The Father with Al Pacino, and had her first starring role playing Snow White against Sigourney Weaver as the Evil Queen, Snow White's evil stepmother, in the folktale-inspired film Snow White: A Tale of Terror. She has appeared in numerous television and movie projects including the TBS Original Movie First Daughter and Crime and Punishment in Suburbia which appeared at the 2000 Sundance Film Festival.
Monica appeared in the film While You Were Sleeping with Sandra Bullock, The Simian Line with Harry Connick Jr. and Lynn Redgrave, and Bad Girls From Valley High. In 2003, she played the heroine Lori Campbell in Freddy vs. Jason. In 2006, she played Celia in the film Left in Darkness.
Keena had a recurring role as Abby Morgan on Dawson's Creek and a starring role on the short-lived Undeclared as the college student Rachel. Keena also had guest roles on series such as Law & Order, Law & Order: Criminal Intent, Homicide: Life on the Street, Feds, and Entourage. On the hit ABC medical drama Grey's Anatomy, she appeared in the second season episode "Into You Like A Train" in which she played Bonnie, a patient who was severely injured in a massive train accident. She later reappeared in the third season episode "Some Kind of Miracle" to reprise her role as Bonnie.
Keena appears as Maddie Curtis in Adam Gierasch's straight-to-video 2009 remake Night of the Demons.