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On one adventure, Jessica battled the Viper and the Silver Samurai. Viper tried to convince Jessica that she was her mother, and when the power behind her latest plot was shown to be the demon Chthon, Viper betrayed Chthon rather then hurt Jessica, and the two went their separate ways. Later, Jessica would be attacked by the Viper, who believed that Jessica had brainwashed her into thinking she was her mother. With the help of Captain America, Jessica defeated the Viper, who fled.

When an insurance company hired her to investigate a rash on industrial robberies in San Francisco, she encountered the Atom Smasher and his henchmen and traced the thefts to Los Angeles. Once there she came across the Thing and Bill Foster (then, the third Giant Man) from whom the Atom Smasher and his men had stolen equipment from. The Thing didn't remember meeting her before but knew she seemed familiar. Together they tracked them down and they learned that Atom Smasher planned to use a neutron bomb to kill everyone in the city and loot it, then blackmail the nations of the world to prevent it from happening to any other city. During the fight the Thing learned that Spider-Woman was immune to the Atom Smasher's radiation blasts. He informed Giant Man, who was dying of radiation poisoning. She donated in a massive blood transfusion to save Giant Man's life, even though the doctor's told her she no longer would possess her immunity to radiation by doing so.

Jessica was then contacted again by Magnus, who convinced her to travel in astral form with him to sixth-century England to free souls from the clutches of Morgan Le Fay. Morgan apparently died in the ensuing battle, although her astral form survived. Morgan's astral form placed a spell on Jessica's prone body, so that Jessica's astral form could not return to it. The Avengers and Doctor Strange traveled to the astral plane to battle Morgan Le Fay and reunite Jessica's spirit with her body. They were successful, but Jessica apparently lost her powers when she returned. She gave up her Spider-Woman identity but resumed her private investigator career.

At one point, Jessica set up operations in the east-Asian city of Madripoor. She was later ensorcelled by the Black Blade to battle the X-Man Wolverine, where it was revealed that Jessica's powers may not have been permanently lost. She would then assist Wolverine on several adventures.

Later still, having somehow become trapped in a magical dimension, Jessica was rescued by Lindsey McCabe, Spider-Man, and the second Spider-Woman, Julia Carpenter.

Some time later, Jessica Drew was attacked by a costumed villain calling herself Spider-Woman, stealing Drew's (apparently fully regenerated) powers for herself. Drew joined with the second Spider-Woman, Julia Carpenter, a recently-rejuvenated Madame Web, and a new hero calling herself Spider-Woman to track down this villain, who had been stealing powers from these women as well. Ultimately, the newest Spider-Woman stole all the powers back from the villain, leaving Jessica Drew without her powers yet again.

Drew remained in New York, and, alongside Madame Web, often helped the new Spider-Woman, a youth named Martha "Mattie" Franklin, in her nascent adventures. Eventually, Jessica Drew began to notice that different aspects of her superhuman powers were returning. Nevertheless, Drew remained reluctant to return to full-time costumed adventuring.