Kara deals with the loss of Mon-El by focusing her energy on being Supergirl and concentrating on a mysterious new threat. Alex confesses a secret to Maggie. A citizen of National City has a mysterious connection to Kara. Lena makes a bold move.
Kara and Alex head home to Midvale for a little R&R. While there, Kara recalls a painful memory of a childhood friend's death and how that traumatic experience brought the Danvers sisters closer together.
Supergirl and Imra have different ideas on how to stop the third Worldkiller, Pestilence. However, when both Alex and Winn are seriously injured by Pestilence, Supergirl and Imra team up to stop the destruction.
Still reeling after learning about Lena's secret, Supergirl asks Guardian for a favor that could alter his relationship with Lena forever. Meanwhile, with all three Worldkillers united, Supergirl and the team brace for an epic battle.
Supergirl learns the true depth of Selena's nefarious plans for Earth. Supergirl, Mon-El and Alura must devise a plan to stop her before Selena gets to Earth. J'onn prepares to say goodbye to his father.