Samantha Maxis was, reportedly, born to Ludvig Maxis and his unknown wife on November 5th, 1934. After his wife died in child birth, Maxis made sure she was always close to him. Due to his research, however, he neglected her and failed to notice Richtofen's experiments on her. As the experiments went on, Richtofen discovered more about Samantha Maxis as he learned more he grew to hate her and Dr. Maxis, perhaps due to Maxis' attachment to her or due to what she and Maxis had become. When Richtofen trapped Samantha in the room with Fluffy, her dog, and activated the teleporter, she was teleported to Griffin Station. There in a panic she accidentally came in contact with the M.P.D and took control of the zombies. In an effort to stop her and free her so that Richtofen could operate it, Groph and Schuster found and brought Maxis to her. However, Maxis told her to kill them all and killed himself shortly after, sending Samantha over the edge and on a rampage to destroy all of the Group 935, which had betrayed and essentially killed Maxis. After Richtofen trades bodies with her to control the zombies, she and the super soldier test subjects activate Maxis's backup plan and incinerate the earth, leaving Richtofen trapped in her body and able to control the zombies on the Moon and the remaining zombies on Earth.
After the events of Moon, Samantha is left in Richtofen's body until her father's plan can come to fruition ten years later. After the final polarization device is activated in Maxis' favor in Buried, Samantha's soul is taken to Agartha with Maxis where she sees the dark Aether's affect on him. She then contacts an alternate version of her father in a Group 935 excavation site in Northern France in Dimension 63, asking for him to free her. After the zombie outbreak at the site she convinces Tank Dempsey, Takeo Masaki, Nikolai Belinski and Edward Richtofen to free her from Agartha.
After being freed from Agartha her soul travels with Maxis to The House where she lives in a perfect universe along with her father, Ludvig, and the child versions of Richtofen, Dempsey, Nikolai, and Takeo. It is here where Monty uses his power to free her of the corruption of the Aether. After some time staying in the House with Eddie (Richtofen's soul), the Souls of the Ultimis Crew are turned into children and also spend some time with Samantha and Eddy until the Primis Crew arrive with the Summoning Key, in which the Shadowman resides and uses it to invade the 'Perfect Universe', and a massive Final Battle ensues between Primis and the Apothicons aided by the Zombies.
After the cycle of the universe is broken, Samantha and Eddie are teleported away from the house by her father, Maxis, to Camp Edward to prevent Monty from killing the both of them. Within the teleporter, she watched her father be devoured by the ancient Keeper, and unleashed her powers when arriving at Camp Edward in a fit of rage. She proceeds to give a speech about how her and Eddie will fight in The Great War and kill Doctor Monty. She accompanies Primis and Ultimis into a forest, where the adults of the group celebrate and pass out drunk, save for Ultimis Richtofen and Primis Nikolai. She and Eddie are pulled away from the rest of the crew by Nikolai, who proceeds to ask her to kill the "one who perpetrated all of this", with Eddie cowering behind her. When Victis gathered the Agarthan Device for Primis Nikolai, Samantha stood by as she saw the rest of Primis and Ultimis lying dead on the floor, poisoned by the alcohol they had previously consumed. After killing Undead Richtofen with a Welling, Nikolai handed the revolver to Samantha, with the clear intent of wishing to be shot. Before shooting Nikolai, Samantha asked Eddie to look away. After killing Nikolai, the dimension the children were left in was plunged into the Dark Aether. Fortunately, Samantha and Eddie were able to walk out of the Dark Aether into a new, uncorrupted universe, free from the effects of Element 115.