In 70 BCE, Bayek of Siwa visited the temple with Aya and Tuta, a street urchin he met in Zawty. There, Bayek consulted Nitokris for the whereabouts of his father, Sabu, but was instead directed to his friend, Kensa, who was in the city.
Years later, Nitokris' daughter, Isidora, had succeeded her position as the God's Wife of Amun after her death. In 38 BCE, Bayek, now the Mentor of the Hidden Ones, visited the temple to sought the aid of Isidora regarding the "curse", having being directed by Merti. There, Isidora directed Bayek to visit a village outside the city which still worshipped Akhenaten and Aten.
In 1340, Egyptian Templars fled to the now-decaying Karnak after stealing the Scepter of Aset from the reigning Sultan, Al-Nasir Muhammad. The next year, the Egyptian Assassin Numa Al'Khamsin and his apprentice Ali Al-Ghraib encountered the Templars at the temple complex.
- Assassin's Creed 5: El Cakr (first appearance)
- Assassin's Creed: Desert Oath
- Assassin's Creed: Origins – The Curse of the Pharaohs