Manny and Lo revolves around the adventures of two orphaned sisters, ages 11 (Scarlett Johansson) and 16 (Aleska Palladino), who have run away from their foster homes. They live in empty model homes, steal junk food from mini marts, and check milk cartons to make sure their photos are not among those of runaways.
"We just stuck to Lo's number one rule," says Manny who narrates the story. "Keep moving and you won't get nailed." However, they are forced to settle down in an empty vacation house when Lo discovers that she's pregnant. Since she doesn't have a clue on how to handle what's happening to her, Lo orchestrates the kidnapping of a clerk in a maternity boutique.
Elaine (Mary Kay Place) is a lonely religious woman whose life is as empty as those of her captors. Despite the fact that bicycle chains are locked around her ankles, she becomes a surrogate mother for the wayward sisters. At one point, Manny asks in voiceover, "Did you ever dream about someone before you saw them in life?" In the eyes of writer and director Lisa Krueger, these three are meant for each other.
Manny and Lo is an oddball charmer about the quirky way certain people are put together just when they need each other most.