A young mutant who ran away from her family and was taken in by Mystique and Destiny as foster mothers, becoming a member of the former's Brotherhood of Evil Mutants and eventually leaving them to join the X-Men. Unable to control her powers for the majority of her history, she was forced to avoid touching others at all cost in order to avoid draining their energy, though when faced with a combat situation this power became a major asset, allowing her to temporarily absorb the powers and even memories of her adversaries. She would later go on to marry fellow X-Men member Remy "Gambit" LeBeau, though the two have currently separated.

The younger sister of the X-Men's Colossus, Illyana was kidnapped by the demon Belasco at a young age, to be tortured and later trained as his apprentice in Limbo. After years, she finally overthrew Belasco and returned to Earth, creating the Soulsword from her own life force and later returning to become Limbo's queen and Sorcerer Supreme. However, her experience had greatly changed her, and losing control of her emotions risks drawing out the demonic entity with which her soul is fused, known as the Darkchylde.

A young member of the X-Men with the ability to change her density at will, allowing her to phase through walls, walk in midair, or allow physical attacks to pass through her harmlessly. Longtime friend and roommate to Illyana, due to being roughly the same age after Illyana's accelerated aging from time dilation in Limbo.

One of the X-Men's earliest members, and the team's leader for many years. After being orphaned by a plane crash and becoming a child thief in Cairo, her mutant power to control the weather manifested, and she came to be worshipped as a goddess until she was recruited to the X-Men, eventually becoming one of their most powerful and prominent members, a member of the Quiet Council of the mutant nation of Krakoa, and the wife of Wakanda's ruler, King T'Challa.

A failed genetic clone of James "Logan" Howlett, who was stabilized with the DNA of and carried to term by the lead researcher on the revived Weapon X project, Sarah Kinney, becoming the biological daughter of the two. After a rocky start in escaping the control of her creators, she joined the X-Men at her father's recommendation, following in his footsteps as the second Wolverine.

The Spider-Woman of Earth-65C, who was bitten by a genetically engineered spider which granted her powers. Falsely branded a criminal for the death of her best friend Peter Parker, and would later become an integral player in various multiversal conflicts.

A genetically modified female clone of Earth-1610's Peter Parker, who retained his memories and abilities. While she initially struggled with her identity due to her memories of life as Peter, she eventually grew into her new identity as Jessica Drew, her universe's Spider-Woman, and would later mentor Miles Morales after Peter's death.

A young girl from Earth-14512 who followed in her late father's footsteps as the protector of New York, forming a psychic link with the spider that controlled his SP//dr mech suit and later becoming an integral player in various multiversal conflicts.

After being bitten by the same irradiated spider that bit Peter Parker, Cindy was taken in by an elderly Spider-Totem named Ezekiel Sims and trained to use her powers. When Sims realized that the totemic vampire Morlun was on the move, he hid Cindy in a bunker to keep her safe, where she reluctantly but willingly remained until she was freed by Parker 13 years later, becaming the hero Silk.

During her early years of high school, Charlotte Webber was bitten by a radioactive spider, becoming the hero Sun Spider. Due to her hEDS, she was an ambulatory wheelchair user in civilian life, and built her webshooters into a pair of crutches, utilizing her newfound powers alongside the additional flexibility caused by her condition to protect the city alongside fellow heroes such as Histamina, who she was initially unaware was her crush Aster.

Shortly before the death of Earth-1610's Peter Parker, Mia Morales was bitten by a genetically-enhanced spider created by Osborn Industries, gaining similar powers to the original Spider-Man along with some unique powers of her own. While she initially rejected the role, she was galvanized by Parker's death to take up his mantle, and would later be mentored both by his clone Jessica Drew, and by his Earth-616 counterpart.

A Czech-American ex-CIA mercenary who developed Dissociative Identity Disorder after being attacked as a child by a Nazi serial killer who pretended to be a friend of his father, a Jewish rabbi. After objecting to an employer's brutal attacks on civilians, he was killed in retaliation and his corpse was left at the foot of a statue of Khonshu, who revived and empowered him as his Fist, the Moon Knight.

Marc serves as the muscle behind Moon Knight, providing his combat experience and extensive military training as the primary member to wear the mask during operations.

Steven manages Moon Knight's finances, leveraging his experience as an investor to finance the system's operations with a fortune built through insider trading on Marc's mercenary operations.

Jake works as Moon Knight's intelligence division, building connections with informants through his New York taxi business and local community reputation.

A member of the Canadian team Alpha Flight who developed dissociative identity disorder due to mutophobic abuse in the Catholic orphanage she grew up in, with Jeanne-Marie holding most of the memories of their abuse and Aurora retaining control over the system's mutant powers. Despite a rocky relationship due to differing values between the two alters, they were able to become a vital member of the team alongside their long-lost twin brother, Jean-Paul "Northstar" Beaubier.

Mary Jane is the host of the Venom symbiote, and the ex-wife of Peter Parker. While operating as the hero Jackpot, the bracelet that granted her powers went haywire and began destabilizing her body, forcing her to permanently bond with the dying Venom symbiote in order to save both their lives.

Venom is an alien symbiote from the planet Klyntar, formerly bonded to Peter Parker and Eddie Brock among others. After being poisoned and presumed destroyed in the aftermath of the Venom War, it hid itself in the sewers until it was rediscovered by a dying Mary Jane, permanently bonding with her in order to save both their lives.

The daughter of master thief Walter Hardy, Felicia trained under her father's mentor, the Black Fox, and became an infamous burglar in her own right from a young age. After encountering Spider-Man while attempting to free her dying father from prison, she became both romantically and professionally involved with him, slipping back and forth between continuing her beloved thievery and aiding him in crime fighting.

A child assassin trained as a Widow by the Red Room, Yelena was assigned as part of a cover family for Alexei Shostakov (Red Guardian) and Melina Vostokova (an older Widow), along with Natalia Romanova, though she was unaware of the mission due to her age and came to view them as her real family. After Natalia defected from the Red Room and became an Avenger, Yelena defected as well and tracked her down in Morocco, later becoming a member of the Thunderbolts / New Avengers after her adoptive sister's death.