Legend tells of a mysterious artifact known as the "Skull Heart" that has the great power to grant a young woman's wishes. Of course, there's a catch. If she has an impure heart, even a selfless wish will be twisted in the vilest of ways. Hundreds have sought the Skull Heart, but so far none have been deemed worthy and spared its cruel power. Those judged impure are transformed into the fearful instrument of their own twisted wish… a pale and lovely tempest and a beautiful nightmare: the Skullgirl!

After the deaths of Queen Renoir, Marie, Filia, Parasoul, Valentine, and other chosen Skullgirls, an thirteen year old girl resembles as Marie named Melissa entered the Grand Cathedral as she ran away from the Medici agents that were chasing after her. She let out a gasp as she glanced at the colored glass windows that the images of three women. Feeling the pain of her chest, she walked the steps up to the altar and stared at the statue of the three women combined into one entity that towered to the high roof of the church.

"Welcome to your destiny, dear child."

Melissa was totally shocked that someone else was there. It was a nun named Double, whose hands pressed lightly together at the palms with eyes closed and head slightly bowed as if she was an image of serene prayer.

"You don't need run anymore, child. The trinity has heard your cries and wants to fulfill your true destiny." Double stated.

Slowly, Double spread her hands and extended them to Melissa that reveal a strange hovering object in a form of a skull cloaked in a blue glow as the light itself sent out an warm feeling toward Melissa as if it was trying to hypnotize her to place her hand on it.

Suddenly, a warm feeling rushed through her vein as if it seemed to spread to every part of her body. As Melissa touched the Skull Heart with one touch, they felt their same emotion: anger and hatred. Maybe Melissa has a true destiny after all.

"What is your wish?" Double asked as she gave Melissa a dark smile.

"I wish…to…have beauty and youth forever." Melissa replied.

Hearing her wish, the Skull Heart sent out a harsh feeling to whirl around Melissa. Her entire body was changing into an impure girl because of her "impure" wish. Her white hair and skin became pale, her red eyes had changed into two skull irises with dark lines under them, a skull and bone motif to her black silt dress outfit, and the Skull Heart was attached in her exposed back surrounded by blue flames as she became becoming the next Skullgirl in the process.

Once the process was complete, the Medici agents arrived in time to capture Melissa. But they quickly turned back around…not long until Melissa releases the power from the Skull Heart to destroy them and add them to her army.

Many years later, many people fought the Skullgirl but none of them received the artifact. Later on, she realized that the Skull Heart and the Trinity are evil and that they want to destroy the world. She decides to do the same thing. As the years and years goes on, many fighters were struggled to sought the Skull Heart and defeat Melissa…but there's only one small female team can save the world from Melissa's evil plot.