Fracture-related infection following orthopedic surgery, especially in cases of war-related trauma, represents a grave complication. The injuries sustained in war often entail severe damage to soft tissues, including significant impairment of vessels, nerves, tendons, muscles, and result in substantial bone defects. Complicating matters further, these infections often involve multidrug-resistant pathogens, making effective treatment a significant challenge. Optimal management of patients with combat-related trauma and signs of infection necessitates specialized care in dedicated centers. The approach to treatment should be guided by a well-defined algorithm that incorporates appropriate surgical interventions alongside systemic and localized antibiotic administration. In instances where chronic infection manifests after war-related injuries and specific causative agents are not definitively identified, initiating empiric therapy is advisable. A combination of meropenem, colistin, and vancomycin can be a suitable choice for initial treatment. Subsequently, once the causative microbes are identified, targeted treatment can be prescribed based on the susceptibility patterns. This article delves into the primary pathogens commonly found in war-related wounds and provides effective antibiotic regimens based on the specific microorganisms. One promising approach for managing severe war injuries is suppressive antibiotic therapy, which enhances the prospects of successful treatment. The comprehensive strategy outlinedhere aims to mitigate the serious risks posed by fracture-related infections in the context of war-induced trauma, ultimately improving patient outcomes and prognosis.