Abstract Background Early patient assessment is important for surgical decision making in severely injured patients. Moreover it is known that early fracture fixation is beneficial, such as those in stable condition or those who respond well to resuscitation. Aims The aim of this systematic review is to identify parameters that indicate risk factors for an unfavorable outcome and early complications. In addition, we aim to improve decision making and separate patients who would benefit from early versus staged definitive surgical fixation. Methods A systematic review was performed of peer-reviewed articles in English or German published between January 1, 2000, and May 15 2022 (PUBMED) according to PRISMA guidelines. The primary outcome was the pathophysiologic response to polytrauma, including coagulopathy, shock/hemorrhage, hypothermia, and soft tissue injury to determine the treatment strategy with the least number of complications. Articles that had used quantitative parameters to distinguish between stable and unstable patients were combined. Results The initial systematic search for MeSH criteria yielded 1550 publications deemed relevant to the following topics (coagulopathy (n = 37), hemorrhage/shock (n = 7), hypothermia (n = 11), soft tissue injury (n = 24)). Thresholds for stable, borderline, unstable, and in extremis conditions were defined according to the existing literature as follows: Coagulopathy; International Normalized Ratio (INR) and viscoelastic methods (VEM)/blood/shock; lactate, systolic blood pressure and hemoglobin, hypothermia; thresholds in degrees Celsius/soft tissue trauma: traumatic brain injury, thoracic and abdominal trauma, and musculoskeletal trauma. Conclusions In this systematic literature review, we summarize the publications by focusing on the different pathways that stimulate pathophysiologic cascades and distant organ damage. We propose that these parameters can be used for clinical decision making within the concept of safe definitive surgery (SDS) in the treatment of severely injured patients.