Gamemnae: An ancient alien, who with others of her kind, has been safeguarding the Earth from the follies of humanity throughout the ages. Gamemnae aims to use technology to subjugate humans. Gamemnae is cunning, witty, ruthless, and always ten steps ahead of her adversaries. Gamemnae’s agenda puts her into conflict with her would-be allies and on a collision course with Supergirl.
Rama Khan: An ancient alien who can control the four ancient elements — fire, water, earth, and air. Arrogant and willful, Rama Khan has been entrusted to use his powers to protect the Earth from mankind for millions of years but now his agenda puts him at odds with Supergirl as well as Lena Luthor.
Kara's investigation into William Dey's "criminal" activities results in the shocking revelation he is not who she thinks. Meanwhile, the conflict between Malefic and J'onn J'onzz reaches a boiling point.
On the eve of the worldwide launch of Andrea Rojas's VR contact lenses, Kara and William team up on an investigation that exposes a terrorist plot. Kelly and Alex celebrate an anniversary, but Alex’s safety is in jeopardy.