She discovered a substance that altered DNA that was highly addictive, using little girls as hosts, before developing compassion for them and attempting to save them from their parasites.

[2] During the events of BioShock, Tenenbaum crosses paths with the protagonist Jack, and she implores him to rescue the Little Sisters, which are guarded by Big Daddies.

She collaborates with Sofia's daughter, Eleanor, who has a psychic connection with the Little Sisters, and asks Tenenbaum to help awaken a Big Daddy called Subject Delta.

Tenenbaum aims to cure the dependency on ADAM and succeeds, leaving Delta to be guided by her ally Augustus Sinclair after she departs.

[2] Tenenbaum's story is continued in BioShock 2's DLC Minerva's Den, set shortly after she parts ways with Subject Delta in the main game.

In it, she works together with the Big Daddy Subject Sigma, formerly Charles Milton Porter, in order to retrieve the schematics of the Thinker, Rapture's operating supercomputer set within Minerva's Den, the city's technology center now controlled by the insane Reed Wahl.

Writer Juho Matias Puro felt that she was one of the "most interesting maternal characters" in modern Western video games, discussing how she is a mother figure during her experimentation, but holding more regard for science than empathy.

Nevertheless, he felt she was interesting due to representing both "the caring mother and the twisted, evil version; sadistic instead of nurturing, hurtful and disregarding instead of comforting.

"[5] Authors of the book Beyond the Sea: Navigating Bioshock discussed how being raised in a fascist regime made intimacy an alien concept to her, which lead to her viewing her maternal instinct as an "abomination."

[6] The Guardian staff analyzed Tenenbaum among other female video game characters, describing her as a "disturbing study in motherhood, creation, and amorality.