Mia was diagnosed with autism as a toddler, but her parents took the advice of a teacher and put her in a regular school, which helped her develop important social skills.
In 2006, Mantegna portrayed the character of Grace Conrad in Warner Brothers' winter feature, Unaccompanied Minors.
She was cast as one of the main roles in an American television pilot show Murder Book for Fox.
In 2008, Mantegna made a guest appearance in the Season 3 episode, for television show Criminal Minds, in which her father stars, wherein she portrayed an abducted teen named Lindsey Vaughn, who witnesses her best friend's death.
In 2017, Mantegna reprised her Criminal Minds guest starring role "Lindsey Vaughn", now operating as a drug cartel hit woman.