Keena was born in New Jersey to Mary, a nurse, and William Keena, a financial sales manager. She was raised in Brooklyn, and has an older sister named Samantha. Monica auditioned for acceptance into LaGuardia High School of Performing Arts at the age of thirteen. Although she chose the drama department as her preference, she was accepted in both the dramatic and the vocal arts departments. Soon after starting her classes at LaGuardia, Keena played in her first role in a short film entitled Burning Love.

Keena went on to portray the character 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's wicked queen in the folktale-inspired 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 The Simian Line with Harry Connick Jr. and Lynn Redgrave, and Bad Girls from Valley High with Julie Benz and Jonathan Brandis in his final film role before his death in 2003 (the film was eventually released straight to DVD in 2005). 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. Monica also had guest roles on series such as Law & Order, Homicide: Life on the Street, Feds, and Entourage. On the hit ABC medical drama Grey's Anatomy, Monica appeared in an episode of the second season titled "Into You Like A Train," in which she played Bonnie, a patient who was severely injured in a massive train accident. Monica later reappeared in the third season episode "Some Kind of Miracle," reprising her role as Bonnie.

Before taking a break for new movies and TV, Keena attended New York University as an English major. When she has a bit of extra time on her hands she likes to take writing classes and likes yoga. Keena enjoys reading. One of her favorite authors is William Faulkner. She also likes the books the The Bloody Chamber by Angela Carter, and The Metamorphosis by Franz Kafka. She likes hanging out with friends and says: "I don't do anything physical. I'm lazy.", However Keena does enjoy roller skating with friends at roller rinks.

Some other things Keena has said to have liked are Bob Dylan, the Police, and Tori Amos. Her favorite movie is The Wizard of Oz. She especially admires Judy Garland, of whom she says: "Judy Garland is my favorite. I probably know all her songs and have seen all her movies." Her favorite TV Shows include The Simpsons and Charmed.