Kara is moved by the story of a missing woman named Izzy and decides to investigate despite Snapper Carr's order to leave it alone. Kara takes Mon-El with her to the last place Izzy was seen and the duo find themselves thrust through a portal to another planet, Slaver's Moon, where the downtrodden are sold as slaves. The leader of the trafficking ring is none other than Roulette. To make matters worse, Slaver's Moon has a red sun, which means Kara and Mon-El are stripped of their powers and stuck on the planet with no way home. Meanwhile, back on Earth, Alex blames herself for Kara's disappearance, fearing she's become too focused on her new relationship with Maggie and too complacent in watching out for her sister.

A large bounty is put out on Supergirl and aliens from far and near attack National City intent on taking out the woman of steel. Alex and Maggie run into Maggie’s ex-girlfriend, Emily, who is in town for a week. Hank gets an interesting order from President Marsdin.

When multiple children get sick from lead poisoning, Morgan Edge points the finger at Lena and blames her creation of the lead bomb she made to save National City from the Daxamites. While Lena knows she never intended any harm, she fears there may have been a flaw in her design, leaving her responsible. Kara teams up with Samantha to clear Lena’s name, but it turns out to be harder than they thought. Meanwhile, Alex and Maggie make a crucial decision about the future of their relationship.

Nia has a powerful dream about Agent Liberty but refuses to look at it as a prophetic dream and pushes it aside. After noticing something is bothering Nia, Kara enlists Brainy's help, and the two try to persuade Nia to embrace her destiny. Meanwhile, Manchester Black pays Ben Lockwood a menacing visit.