It's autumn 1888, and Jack the Ripper is on the run. As London police close in, he flees England for New York City seeking new victims. But a primal force of female vengeance has had enough. With serpents for hair and a fearsome gaze, an awakened Medusa is hunting for one thing: Jack.

And other dangers lurk in Manhattan's Bowery. Salvation Army volunteers Tabitha and Pearl discover that a girl they once helped has been forced to work in a local brothel. Tabitha's an upstate city girl with a wry humor and a thirst for adventure, while farmgirl Pearl takes everything with stone-cold seriousness. Their brittle partnership is tested as they team up with an aspiring girl reporter and a handsome Irish bartender to mount a rescue effort, only to find their fates entwine with Medusa's and Jack's.