Sara Pezzini and her partner Danny Woo are once again in pursuit of the allusive mobster Tommy Gallo. As before, Tommy's henchman lures Sara into the museum where she encounters the Witchblade and it claims her as its chosen wielder. This time, however, things are different. Though it's a case of deja vu as she retraces her steps to the Rialto Theater, an older and wiser Sara declines the opportunity to confront Gallo inside. Although the past may be altered, Kenneth Irons has plans for the future and he determines to take the Witchblade from Sara even if it means having her killed. A much conflicted Ian Nottingham finds his loyalties split between guarding the chosen Witchblade wielder and carrying out the wishes of his master/father, Irons. Using an online murder/hit as bait, Irons lures Sara into his clutches while promising an ambitious and cold-blooded woman named Cristina that she will wear the Witchblade if she takes out Sara. To do so, Cristina must first get rid of Danny so she buries him alive, leaving him to die a horrible, slow death. In a Witchblade frenzy, Sara kills Cristina before she can make her tell what she did with Danny. As her partner runs out of air in an unmarked grave, Sara desperately searches for him before it's too late.

As Sara and Danny investigate a series of bizarre drug-related murders, rookie detective Jake is pulled into a sting with a questionable cop. Now Sara must learn to use the Witchblade to solve the crime and save Jake before it's too late.