Kara isn't featured much in this episode due to her being captured by Cadmus. It was specifically written for Kara to get captured so that Melissa Benoist could film Invasion! (2016), Invasion! (2016) and Invasion! (2016).
While discussing the Guardian, Kara says that her cousin worked with a masked vigilante "with a lot of gadgets", referencing Superman's partnership with Batman.
It is not addressed how Lillian knew the Medusa virus was being kept at the Fortress of Solitude so the Cyborg Superman could retrieve it. Brenda Strong suggested "the underground intelligence world...I think she's a scientist, so I'm sure there are things about alien life forms that she's aware of. I think whenever you have a single-minded purpose (...) you'll do anything, and I'm sure she has a lot of people who aren't fans of Superman and Supergirl to aid her in her destruction."
The Solar Flare Supergirl is forced to use, rendering her temporarily powerless, is a new power for kryptonians that first appeared in the comics with the New 52 version of Superman during the run of John Romita Jr. as artist.
Lillian Luthor's description of her son is a version of Lex Luthor's origin story that is consistent with his appearances in the Silver Age comic books. The same story was adapted for Smallville (2001). In the comics version, Luthor and Superboy were childhood friends until a mishap involving the latter inadvertently caused Luthor's baldness. In Smallville (2001), the two are friends until Luthor grows paranoid about the existence of aliens on the planet.