The third Worldkiller, Pestilence, begins striking down the citizens of National City.... including Winn and Alex. Supergirl and Imra disagree on how to deal with Pestilence, and Lena continues trying to find a cure for Sam.

Lena provides Alex with a safehouse to protect Ruby from Reign, who is looking to severe the last ties of humanity that Sam has with her family. Meanwhile, Supergirl discovers that Lena has been manufacturing Kryptonite, and the Legionnaires depart for the future.