Samantha began her career as a nurse at Walter Reed Army Medical Center in Washington, D.C. She was then transferred to the George Bush Center for Intelligence in Langley, Virginia for three years to work on the CIA program Operation Treadstone. She helped train several assets, including Doug McKenna and Vincent, and she worked with Treadstone officials such as Leo Biller, Anna Collier, and Lowell.
Despite training over a dozen assets, she took especial interest in Doug McKenna because part of his original personality bled through his asset training in the form of a look in his eyes. After releasing him to assume his cover life, Samantha waited a year before reintroducing herself to him, claiming to have come from Boston, which was actually Doug's own hometown that he no longer remembered. Doug and Samantha fell in love and married, with Samantha herself assuming that he would never be called in for a mission due to Operation Blackbriar being shut down.
Doug mysteriously returned home early from his job in the Arctic, having been laid off in favor of a Russian team. Samantha welcomed him back and advised him to continue taking his medicine regularly, which help keep his old memories suppressed and reduce his headaches.
The next day after work Samantha went day drinking with Doug at Cloonie's Bar in Huntington, West Virginia. Lowell followed them home and attacked Doug when Samantha went upstairs, but hearing the fight she came back down with a gun in hand. She arrived to see Doug held at gunpoint, so she shot Lowell in the head, killing him and saving Doug.
Realizing that she just killed a Treadstone agent attempting to perform his duties, Samantha began to panic and quickly rejected Doug's idea to call the police. This confused Doug as he had no memory of Treadstone or just how far-reaching it was, and although he asked Samantha how Lowell knew her, she claimed to have never seen him before. Doug relayed his experience in the Arctic of having a memory blank and waking up with blood on his hands, which Samantha recognized as asset activation but tried to brush over. Samantha desperately convinced Doug not to report Lowell's death to the authorities so that they would not be separated, and when Doug suggested disposing of the body, Samantha offered to help.
In the woods Samantha started to dismember Lowell's body, removing his hands, feet, and teeth to obstruct identification of the body. This unnerved Doug, but Samantha brushed it off as part of her nursing career and focused on questioning Doug a strange woman he met in the Arctic. Doug eventually recalled that the woman sung a nursery rhyme, which confirmed to Samantha that Doug had been awoken and deployed on a mission. Eventually Doug questioned how Samantha learned to shoot so accurately, but she brushed it off as mere luck. They then finished dismembering and burying Lowell.
Back at home Samantha went to find bleach to clean the blood, but returned to find Doug looking over Lowell's suitcase. Inside were floor plans and a target package for Patty Vernon. She found a post-hypnotic trigger for a kill mission for Vernon, and Doug revealed that he had an identical photo of his own, making Samantha absolutely certain that Doug had been deployed on a kill mission. Faced with the undeniable reality that Operation Treadstone was alive and well, Samantha decided to reveal everything to Doug.
Samantha revealed that she actually worked in Washington, D.C., not Boston, before being transferred to a CIA facility to train assets for Operation Treadstone. This included Doug himself, although Doug had no memory of it, which she said was an intentional part of the training. Although Doug disbelieved her, Samantha insisted that his entire identity was artificial, a cover story for him to go into deep cover. She said she had no intention of ever telling him this and only wanted to "protect us", to which Doug said "us is a fucking lie, Sam".
After wrestling through the emotional sucker punch, Samantha went after Doug and explained what the photo he woke up with was: it's a "post-hypnotic trigger" to zero-in his subconscious on a mission after being awakened with Frère Jacques. She explained that his subconscious will always see it as a problem to be solved until he completed his mission, which in this case is to kill Patty Vernon. Samantha also insisted that the CIA would continue sending soldiers to capture or kill Doug so long as the mission goes uncompleted. Finally, Samantha revealed that his dreams were actually memories, and that the reason why he responds to Frère Jacques is because she herself sung it to him during the training process.
Doug relented and agreed to perform the mission, so Samantha drove him out to meet up with a heist crew to perform it. While waiting for their arrival Doug asked Samantha about other assets in Treadstone, to which Samantha said that Doug was the seventeenth that see herself trained. She also revealed why she married him, his old self manifesting in a look in his eyes, and then returned home when the heist crew arrived.
The next day Samantha found Doug outside on the porch after the mission. He was unnerved by what he was capable of and mentioned that Samantha and the CIA turned him into a monster. At Doug's questioning, she revealed that she wasn't from Boston, and that Boston was in fact Doug's own hometown. Doug then mentioned that Mike was at the pill factory with Patty Vernon, so he made to leave to talk with him. Just before he left Samantha asked if they were "ok", to which Doug said he didn't know.
While Doug was gone Samantha prepared to flee CIA pursuit, buying a new car in cash, changing her hairstyle, and preparing go-bags for their departure. Doug arrived to warn her about the CIA sending a team after them, but she had already surmised as much and was ready to leave. They then hit the road, with Doug telling Samantha about Treadstone's intention to send another asset to kill Marcus Sachs and his wife.
Samantha researched the pair and discovered that Marcus Sachs was a rare-earth metal geologist who lived in Arlington, Virginia. Doug proposed going there to save him, but Samantha cautioned that the presence of another asset there would make the area incredibly dangerous. Doug insisted on attempting to save Sachs anyway, but shortly after he entered Sachs' house an explosion blasted through it. Samantha then ran in to help Doug.
Samantha arrived to see Doug fighting Vincent, and managed to tackle Vincent when he pulled a gun to kill Doug. Vincent shrugged her off and prepared to shoot her, but she stalled him by evoking his name, dragging up memories from before he became an asset for the CIA. This hampered him just long enough for Doug to close to grappling range and renew the fight, so Samantha moved to the badly wounded Mrs. Sachs to try and keep her alive.
When Marcus Sachs was shot by Vincent, he dragged himself over to Samantha where she tried to keep him alive as well. Unfortunately Samantha wasn't able to save them, and they died together just as Doug managed to kill Vincent. This terrified Samantha, who thought they'd end up dead just like the Sachs'. She gave into despair and claimed that running would be useless as Leo would report that Doug is still alive, which gave Doug an idea to steal Vincent's identity and fake his own death. Samantha helped Doug destroy Vincent's body when they received orders (posing as Vincent) from Treadstone to destroy Doug's body.
Later, Samantha announced her intention to return to Treadstone to figure out what was happening, saying that they'd want to question her before thinking about killing her. Doug objected strenuously, but Samantha assured him that she'd improvise, and that it would all end when they knew they were safe. At Vincent's residence Samantha began a running dialogue about Vincent's backstory and cover life so that Doug could mimic him. While doing this Samantha discovered his cache of weapons and Doug discovered his cache of money, passports, etc.
Samantha then gave Doug a "pharmacological neuro-receptor antagonist" drug that would ostensibly allow Doug to resist the compulsion of his Treadstone programming. Afterward they set up a dating website account to communicate by editing a single draft with messages. Samantha also revealed to Doug that when she left Treadstone in the aftermath of Operation Blackbriar being shut down, she decided to give Doug a year to develop his own personality before reintroducing herself to him. She expressed how sorry she was for what she made him into, but Doug forgave her and then they had sex.
The next day Samantha reached out to Treadstone. She assured Doug that Treadstone would want her back in to ensure that no other assets were "glitching" like Doug did, and although Doug warned that they would kill her if they discovered that he was not truly Vincent, she insisted on going through with it anyway. She kissed Doug and then left to be picked up by Leo Biller. She left a message for Doug on the dating website draft that Leo did not trust her.
Leo then met with Samantha to figure out what her "angle" was, to which she claimed to only be looking for her husband Doug. She lied to Leo that Doug killed Lowell and then vanished. Leo then left, and when he returned he claimed that Doug was dead, so Samantha pretended to be distraught. She demanded to be let out, but was interrupted by the arrival of Anna Collier, who told Leo that "Vincent" missed his target window to kill Padre Vicuna. Leo and Anna then left to deal with the situation, so Samantha reported the worsening situation to Doug via the dating website.
Samantha then followed after Anna and Leo to offer "help", suggesting that Vincent's serotonin levels might be at fault for his failure. However, Anna reported that his finished his mission, so Samantha asked where "Vincent", Doug, was. Leo reported that he was in Colombia, as a mining company wanted to acquire a deep vein of rare-earth metals located on protected native lands, so Vincent was dispatched to assassinate their leader Padre Vicuna in order to clear the way for the company. Samantha was disturbed by the fact that Treadstone would work for a private company, but Anna justified it as the simple process of securing resources for America as the population skyrockets and goods become scarce.