The successor of King Taharqa, his uncle or cousin, Tanutamani pursued the policy of opposition to the Assyrians' aggrandisement at Egypt's expense. Initially he was successful, traveling down river and subduing or conciliating those who had supported the Assyrians or who still resented Kushite rule. He eliminated those in the Delta who had compromised with the Assyrians, and the chiefs of the region surrendered to him.

But calamity was imminent; the Assyrians, after an initial defeat, regrouped and poured into Egypt. They sacked the sacred city of Thebes and pillaged its legendary treasure. Tanutamani fought back but was driven further and further south until he had no recourse but to withdraw to Nubia; there he remained. He was the last king of the Kushite dynasty to rule Egypt, though members of his family were kings in Nubia for many years to come.