3x3 Eyes is a story that follows the adventures of Pai, the last remaining Sanjiyan Unkara, and her new Wu (Chinese reading of 无; an immortal companion), Yakumo, as they desperately try to find a way to make Pai human so that she can forget her troubled past. Yakumo can again become mortal and end his constant need to protect Pai because if Pai dies, then so will he. Along the way, they encounter many followers of the now-dead demon god Kaiyanwang, all of whom wish to kill Pai or siphon off her power in order to resurrect their deity and/or gain immortality.