During the Clone Wars, she was one of the Nightsisters to discover and Asajj Ventress, a former Nightsister who had been betrayed by Count Dooku. She, along with other Nightsisters, prepared to kill Ventress, only to be stopped by Talzin, who told her clan that Ventress was one of them. She then with Talzin had Water of Life to revive Ventress from the dead. Then she and a few other Nightsisters had invisibility potion and used it to infiltrate and trick Dooku.
She saw Dooku's arrival at her fortress. Some time later, Talia, Karis, Talzin, and a manipulated Savage Opress used a Sheathipede-class transport shuttle to travel to Dooku's castle to deliver Savage to Dooku as a replacement apprentice.
Later in the war, when Asajj Ventress returned to Dathomir to rejoin the Nightsister clan. Count Dooku however wanted Ventress dead and ordered the massacre of the entire Nightsister clan. By the end of the fight, Talia, and all of the other Nightsisters, save for Ventress and Talzin, were killed.