Hunting down the Rhino as Venom, Gwen became increasingly aggressive and violent as the symbiote's influence over her grew.

Now living in the 616 reality, upon Julia Carpenter's warning an unknown force brought Spider-Man (Peter) into conflict with Sin-Eater, Gwen told him that she didn't really how her counterpart would think about Norman Osborn.When a fire truck went past the diner, Gwen bid her father farewell and left to assist the firefighters in evacuating a burning apartment building.

Despite Captain America's support and her father issuing a public confession of how poorly the Spider-Woman investigation was handled, Gwen became depressed at the prospect of permanently losing her powers once her eight isotopes were used up. Saying she should talk to Peter Parker, having never personally met Gwen Stacy herself, Jessica advised her to focus on being the best Gwen Stacy she can be rather than dwelling on what happened to Earth-616 Gwen and Earth-65 Peter. However, she also acknowledges that it is a living creature that is her responsibility, and she has taken it upon herself to show it a better path alternative to the more destructive nature its inclined to.Despite her best efforts, she was blackmailed by the Storms into leaving for good, and after bidding her father goodbye, went into self exile in the Prime Marvel Universe. Gwen rejected an offer by Captain America to let her out of prison if she joined a black-ops team consisting of potential assets like Black Cat, Silk, Kitty Pryde, Logan, and the Punisher; stating she needed to be held fully accountable for her actions as Spider-Woman.

When they arrived at Otto's lair, it was already to late, and she witnessed as the Spider-Noir killed himself and Spider-Uk's life energy was absorbed by the Inheritors. Curtis Connors, the only other person aware that Peter had been the original Lizard, but that Connors had vanished after Peter's death.Gwen would eventually get a part-time job at a smoothie shack, where she met Mateo, a guy she had a crush on.