The series follows a group of eight teenagers, who live together in Anubis House (named after the Egyptian god, Anubis), an early 1900s-era building that serves as a boarding house for an elite boarding school in the United Kingdom. Nina Martin (Nathalia Ramos), an American girl who had been living with her grandmother since the death of her parents, leaves the States to attend and move into the school; at the same time, another resident, popular student Joy Mercer (Klariza Clayton), suddenly disappears without warning and the school's strict landlord, Victor Rodenmaar (Francis Magee), attempts to be rid of Joy's existence from the school.
Patricia Williamson, Joy's best friend (Jade Ramsey) is dismayed to discover her friend has left without a trace and accuses Nina, who is her new roommate, living in the same dorm room that Joy stayed in with Patricia, of being involved with Joy's disappearance. Nina later meets a senior citizen named Sarah (Rita Davies), who had lived in the house decades earlier, her parents were archaeologists in Egypt who mysteriously died. In order to get to the bottom of the situation behind the vanishing of her best friend, Patricia forces Nina to spend a night in the attic of the house, as a sort of initiation. Nina later discovers wax cylinders hidden in the attic revealing that the house has a secret history and holds a mystery that is unknown to anyone. She decides to investigate it, alongside her new friend and fellow resident Fabian Rutter (Brad Kavanagh) and another resident in the house, Amber Millington (Ana Mulvoy Ten). They form a group called "Sibuna" or Anubis backwards. The three teens team together to search for the treasure that is hidden within the House of Anubis, and uncover the mystery behind the school as well as the disappearance of Joy, while also dealing with the situations that come with everyday teenage life