Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection, leading to organ dysfunction and high mortality. Early recognition and protocolized interventions are critical for improved outcomes. This narrative review synthesizes current evidence-based strategies relevant to medical–surgical settings, focusing on early detection, fluid resuscitation, antimicrobial stewardship, hemodynamic support, source control, and nursing-led monitoring. It emphasizes the importance of multidisciplinary collaboration among nurses, physicians, pharmacists, respiratory therapists, and dietitians, in alignment with the Surviving Sepsis Campaign guidelines. Persistent challenges such as antimicrobial resistance, delayed diagnosis, and resource limitations are discussed, alongside future directions including novel biomarkers, personalized care pathways, AI-driven early warning systems, and strengthened antimicrobial stewardship programs. Optimized nursing protocols, enhanced interprofessional communication, and advanced monitoring strategies can significantly reduce sepsis-related morbidity and mortality.