Siemaszko was born in Chicago, Illinois to a Polish American father and an English mother. Her brother is actor Casey Siemaszko. Her first feature film was in the 1986 comedy movie One More Saturday Night as Karen Lundahl. Her other well-known role in the 1980s was the 1988 comedy film License to Drive as Corey Haim's sister Natalie Anderson. Nina has starred in many TV movies, especially ten Mystery Woman TV movies, the latest of which is Mystery Woman: In the Shadows.
She appeared in the 1992 hit film Reservoir Dogs as an undercover cop, but her scene in the film ended up in the cutting room floor, though now you can see her scene in the deleted scene section on "Reservoir Dogs 10th Anniversary-Special Edition" DVD.
In 1998 Siemaszko played Mona Ramsey in the PBS miniseries More Tales of the City, the sequel to 1994's Tales of the City (which starred Chloe Webb in the role of Mona), and had a brief role on Sports Night as the Nanny for Casey's son Charlie.