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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