Monica was a brilliant scientist and geneticist working for S.H.I.E.L.D.. Prior to A-Day, she was in a romantic relationship with Bruce Banner. Monica was also working with him to try to understand the gamma radiation that fueled the Hulk. During one of these test an electrical creature was formed and came alive as a result of two S.H.I.E.L.D. Operatives being merged togetherand started attacking . Bruce told Monica to flee to safety as he transformed into the Hulk and engaged the creature managing to stop it by knocking it into the bay. As Bruce regained consciousness Monica greeted him and comforted him.
On the day of A-Day, Monica decided to steal the Terrigen and use the reactor for her own ends. Contacting former SHIELD agent turned mercenary Tony Masters / Taskmaster, she hired him and his mercenaries to steal the crystals for her, using the A Day celebration as a distraction. She spent the eve of the event with Bruce, though left that morning to attend final preparations of the plans.
During the event itself, Monica and George met shortly before they went onstage, unknowingly within earshot of young fan Kamala Khan. As he expressed worries that Stark would take credit for simply funding his work, she reassured him and promised he'd get the attention needed. As the conversation ended, the two were discovered by Bruce, who she apologized to for disappearing. Together, the group were on stage during the main event, alongside the Avengers.
Monica was presumably onboard the Chimera during during Taskmaster's assault on it and the Golden Gate Bridge. According to most reports, she and Tarleton survived the crash by taking shelter on the command deck. Unknown to most, Monica was responsible for Captain America's disappearance, having ambushed him as he recovered and place into cryo-hibernation. She and George were able to avoid most of the fallout of the event, instead focusing on building AIM. 
As the Senate hearings for the Avengers role in the catastrophe of A-Day began , Monica managed to convinced Bruce to testify that the Avengers were a threat, leading to the team's disbandment. After this, the group each went their separate ways, ending the relationship and team of The Avengers. Working alongside Tony Starks rival Justin Hammer, Monica was able to organize the dismantlement of SHIELD and Stark Industries, using the gathered resources to build up AIM's resources. These included research undertaken by the organizations and their facilities, including those within proximity to towns. However, Rappaccini eventually betrayed Hammer, using her resources to gain control of his company and merge it into AIM.
With the new resources, Monica extracted blood from Captain America, using it to create a substance she codenamed the "Regenerative Formula". To prevent discovery, she moved him and her laboratory to the SHIELD space station Ambrosia, hiding the information from everyone even Tarleton. When George went through Terrigenesis due to his DNA and expose to Terrigen mists, Monica used to formula to reawaken him from a six-month coma. Unknown to all but her, it also enhanced his Inhuman abilities and granted him technokinesis, though enlarged his head as a result. With other Inhumans emerging due to A-Day, they used their resources and connections to push their agendas that these powers were a disease on humanity and that AIM could cure them through science.
Through captive Inhumans captured against their will, Monica and George began experimenting on them, learning about their powers and relations to genetics. Through them, they began working on various attempted cures derived from her serums and projects, though they were always unsuccessful or deadly to them. Among these projects was the Dark Terrigen and the power-replicating Adaptoids. Monica's research on the Hulk also allowed her to replicate him, using AIM's Chief of Security, Emil Blonsky, as the test subject. This was successful and allowed him access to his memories and personality something Banner lacked when he transformed into the Hulk. As Monica and George continued their experiments, she also discretely continued testing on him, increasing the potency slowly.
After captured Kamala Khan while she was trying to infiltrate an A.I.M. base to rescue Inhumans, the undercover Black Widow revealed herself, fighting and capturing Monica as well as freeing the captive Inhumans. While on the Chimera, Monica was freed by A.I.M., nearly bringing down the Chimera, before being stopped by Thor. Monica escaped and returned to A.I.M..
After Iron Man broke into the Ambrosia satellite and rescued the captured Captain America, Monica was confronted by Tarleton, who discovered that the regenerative serum given to him was derived from Steve's blood. Angered, Tarleton killed Monica. However, unbeknownst to him, Monica was able to clone herself. After the Avengers had defeated Tarleton, calling himself M.O.D.O.K., Monica took over as Scientist Supreme of A.I.M..