Eliza comes to town to celebrate Thanksgiving with her daughters. Alex decides it’s time to come out to her mother; Kara is shocked when Eliza suggests Mon-El has feelings for her, and Winn and James consider telling Kara the truth about the Guardian. Meanwhile, Cadmus unleashes a virus that instantly kills any alien in the vicinity so Kara enlists an unexpected ally – Lena Luthor. The epic superhero crossover kicks off tonight when Barry Allen and Cisco Ramon seek Kara's help with an alien invasion on their Earth.

The crossover continues on The Flash S03E08 Invasion! (II), Arrow S05E08 Invasion! (III) and DC's Legends of Tomorrow S02E07 Invasion! (IV).

When Mr. Mxyzptlk, a magical imp, shows up on Earth and declares his love for Kara, she tries to let him down easy, thinking him harmless. However, he decides it’s a challenge and starts to wreak havoc on National City. Mon-El has seen beings like Mr. Mxyzptlk on Daxam and knows how dangerous they can be. He and Kara argue over how to get rid of Mr. Mxyzptlk, further straining their relationship. Meanwhile, Alex and Maggie celebrate their first Valentine’s Day together.

With his P.I. shingle newly hung outside his office, J'onn welcomes new clients. Trying to take her mind off what happened at the DEO, Kara decides to team up with J'onn on his latest assignment, which unfortunately ends up tying directly into Alex's current investigation that involves the villain Menagerie. Meanwhile, Lena shares some news with James, but his reaction isn't what she expected. Nia invites Brainy to her Valentine's Day party.