Managing the acute phase after a severe traumatic brain injury (TBI) with polytrauma represents a challenging situation for every trauma team member. A worldwide variability in the management of these complex patients has been reported in recent studies. Moreover, limited evidence regarding this topic is available, mainly due to the lack of well-designed studies. Anesthesiologists, as trauma team members, should be familiar with all the issues related to the management of these patients. In this narrative review, we summarize the available evidence in this setting, focusing on perioperative brain protection, cardiorespiratory optimization, and preservation of the coagulative function. An overview on simultaneous multisystem surgery (SMS) is also presented.