After losing her mother in a tragic car accident, nine-year-old Melmo Watari now faces a big challenge: taking care of her two younger brothers, the preschooler Totoo and baby Touch. Watching from Heaven and concerned about her kids' terrible situation, their mother decides to appear in their lives one last time as a ghost and give Melmo a jar full of magical candies. The candies have the power to make her 10 years older or younger, as well as turn her into any animal she wants. Using her newfound abilities, Melmo wears various disguises as a 19-year-old woman and looks after her brothers, all while still trying to lead a normal life.

In a small town, there is a small pharmacy called Fun Fun Pharmacy. Popuri, a girl who recently moved in downtown, discovers this pharmacy and meets Miss Fukiko, who is actually a witch. Miss Fukiko gives Popuri a mysterious bottle that can create magic spirits.

After Tamahome is reborn into the real world as Taka Sukunami, it does not take long until he meets Miaka Yuuki again, leading to their romance blooming once more. However, the appearance of Ren Shigyou—a new student at Miaka's high school—disturbs their blissful days. Resentful of the happy lovers, Shigyou uses his unusual manipulative skills to quickly become popular and rally his classmates against Miaka and Taka. As Shigyou's followers unexpectedly attack the pair, the two end up falling from the school's roof into a red light and are transported to The Universe of the Four Gods realm. Returning to the place where Taka once lived as Tamahome, the couple learns that an evil demon is behind the recent events. To make matters worse, Taka risks disappearing from existence unless he recovers his previous life's memories, which are stored in seven jewels. Joining forces with their former companions, Miaka and Taka embark on a quest against the clock to retrieve the precious stones before it is too late.

After years of hardships interfered with their love, Miaka Yuuki and Taka Sukunami are finally married and expecting a baby—the pinnacle of their unbreakable bond. Unfortunately, not everyone rejoices alongside the blessed couple. Mayo Sakaki, one of Taka's students, has a crush on him and cannot bear witnessing the pair's flourishing relationship. Upon discovering The Universe of the Four Gods, Mayo learns that the old book is where Miaka and Taka first met as the priestess of the god Suzaku and the god's Celestial Warrior Tamahome. Unscrupulous about destroying a happy family, Mayo readily ventures inside with hopes of becoming the new priestess of Suzaku and rewriting the story to her advantage. Meanwhile, her actions do not delay to show devastating effects. Leaving an unconscious Miaka at the hospital, Taka must follow Mayo to The Universe of the Four Gods and stop her before the circumstances worsen for his wife and their unborn child.