In the year 3000, a mysterious skull was discovered. It's surrounded by bluish flames. No one can figure out where it came from or what's causing the flames. Nevertheless, the mysterious skull attracts visitors. Many people go to see it, even if the scientists prefer it to remain sealed in a secure room.
As Alana looks at it, the skull begins to speak to her. It tells her it's the Skull Heart and can grant any wish. Alana is suspicious. Jenny has taught her well that lies and betrayals exist. Unfortunately, the Skull Heart is convincing and Alana wishes to see Jenny and her family again.
The Skull Heart makes her wish come true. Jenny, her brother Petey and her mother Irene are teleported from 1990 to the year 3000. In exchange, Alana will slowly transform into the evil Skullgirl and destroy the world.
Alana doesn't want to hurt anyone. She asks Jenny to stop her heartbeat with Alana’s Transducer. Jenny doesn't want to kill her. The Skull Heart tells Alana it's no use. The only way she can die is for the Skull Heart to be destroyed and Alana is now "programmed" to protect it. Irene doesn't believe a word of it, but when she tries to grab the Skull Heart Alana bites her hand. Petey in turn tries to take the skull and destroy it. Alana pushes him away.
While crying, Alana asks Jenny, Petey and Irene for forgiveness and flees with the Skull Heart. The Kelly family, Tulista, Lorien, Bruno, Arva and Freya set off in search of her. Alana is nowhere to be found.
A week later, as the Kelly family adjusts to their new life in the future, people report seeing skeletons walking. This upsets Arva and the World’s Council.
Three days later, skeletons are everywhere. The inhabitants of the year 3000 are forced to destroy them with their Transducers, which deals a heavy blow to their psyche, as they are unused to violence. Suddenly, a giant projection appears in the sky. It's a young girl, part of her body fleshless, all bone. Jenny recognizes her. She’s Alana.
Alana announces that she’s the Skullgirl and will destroy the world. She encourages anyone to stop her and destroy the Skull Heart, even if it kills her.
Jenny, with her own Transducer on her forehead, watches Alana's projection and promises to fight her to save the world. After all, Jenny is her best friend. Her mother, Irene, begs Jenny not to do anything, to stay hidden with her and Petey, but she won't listen. Jenny has to stop Alana. She has no choice.