Supergirl must beat a ruthless new gang who has been armed with dangerous new alien technology. When Cadmus sends a video to the DEO, the team realizes Cadmus is the one staffing the criminals for a secret mission. Meanwhile, Kara gets Mon-El a job as an intern at CatCo, James makes an important decision and Lena invites Kara to attend one of her fundraisers.

Armek, a White Martian, descends on National City intent on taking M’gann back to Mars to face her punishment as a traitor. Hank and Supergirl determine the best way to keep M’gann safe is to bring her to the DEO. However, when it is revealed that Armek shape-shifted into M’gann and is now loose in the building, the team realize he could be disguised as any one of them.

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.

Psi, a thief with psychic powers, attacks National City. Able to immobilize people by tapping into their worst fears, Psi proves a formidable opponent for Supergirl. Meanwhile, James and Lena are at an impasse, and Samantha starts her new job at L-Corp.

When Winn and the team discover an alien ship has crash landed deep underwater beneath National City, Kara/Supergirl is called in to investigate. Meanwhile, Hank attempts to bond with his father, Myr'nn. Samantha, eager for some understanding of the changes she has been experiencing, looks to her estranged mother, Patricia Arias, for answers.

As Reign continues to terrorize the city, Supergirl teams up with Saturn Girl, and the two recruit Supergirl’s former enemies, Livewire and Psi, to form a team for a mission to Fort Rozz to recover a prisoner who has information on how to defeat Reign once and for all. Meanwhile, Alex babysits Ruby.

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.

Kara makes a major life decision. Meanwhile, J'onn finds out that special DEO-caliber guns have hit the streets of National City.