Nina Lisandrello was born in Los Angeles to an Italian-Brazilian father and a Afro-Dominican and Native American mother. Because her mother was a singer, she traveled with her around Europe as a child. She was raised in New York City. As a student at NYU's Tisch School of the Arts, she majored in film production. During a course focused on directing actors, Nina fell in love with the acting process and pursued it full-time after graduating. She completed the Meisner program at William Esper Studio, and went on to take master scene study courses with Deborah Hedwall and Wynn Handman. After playing a few guest star parts, Nina landed a series regular role on CW's Beauty and the Beast (2012). After four seasons of playing Tess Vargas, Nina itched to get back behind the camera and be more involved with the creative process and made her directing debut in the film Vacant (2017).
Nina was the subject of a paternity suit involving Robert deNiro. Her mother claimed she was his child, but the courts ruled against her in 1993, after several blood tests.