After splitting up with The Joker, Harley Quinn (Margot Robbie) and three other female superheroes - Black Canary (Jurnee Smollett), Huntress (Mary Elizabeth Winstead) and Renee Montoya (Rosie Perez) - come together to save the life of a little girl, Cassandra Cain (Ella Jay Basco), from an evil crime lord, the Black Mask (Ewan McGregor).