叙利亚沙漠中,女吸血鬼丹尼卡(Parker Posey 饰)带领一队同类,深入古老的沙漠宫殿,意欲唤醒沉睡的吸血鬼之王——德雷克(Dominic Purcell 饰)。夜色中,刀锋(韦斯利•斯奈普斯 Wesley Snipes 饰)仍然与吸血鬼们进行着无休止的战斗,但他很快落入了丹尼卡的圈套,误杀了一名人类,因此被FBI探员威尔逊等人抓捕。与此同时,刀锋的老搭档惠斯勒之女阿比盖尔(Jessica Biel 饰)同汉尼拔金(Ryan Reynolds 饰)等年轻人秉持与刀锋相近的信念,组成了一支以自身为诱饵来消灭吸血鬼的队伍,他们将刀锋从FBI和丹尼卡手中救出,但后者对他们的胆大妄为嗤之以鼻,然而面对强大的吸血鬼王德雷克,他们不得不并肩作战……
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