Background: Surgical site infections (SSIs) remain one of the most common healthcare-associated infections worldwide and continue to contribute significantly to postoperative morbidity, prolonged hospitalization, increased healthcare costs, and mortality. Despite advancements in surgical techniques and perioperative care, variability in infection control practices and compliance within operating theatre settings continues to affect patient outcomes. Effective infection prevention requires a multimodal and evidence-based approach integrating preoperative, intraoperative, and postoperative interventions. Objective: The objective of this systematic review was to evaluate the effectiveness of infection control interventions in reducing surgical site infections and to identify key operating theatre practices associated with improved perioperative outcomes. Materials and Methods: This study was conducted as a systematic review following PRISMA guidelines. A comprehensive literature search was performed across PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar for studies published between January 2000 and March 2026. Keywords included “surgical site infection,” “infection control,” “operating theatre,” “aseptic technique,” and “sterilization.” Randomized controlled trials, observational studies, systematic reviews, and cohort studies evaluating infection control interventions in operating theatre settings were included. Data extraction focused on study characteristics, interventions, and SSI-related outcomes. Qualitative narrative synthesis was performed due to heterogeneity among studies. Results: A total of 48 studies were included in the final analysis. The findings demonstrated that multimodal infection control strategies significantly reduced SSI rates compared to isolated interventions. Preoperative antibiotic prophylaxis and chlorhexidine-based skin antisepsis were associated with substantial reductions in infection rates. Intraoperative measures, including strict aseptic technique, sterile field maintenance, instrument sterilization, and operating theatre traffic control, were identified as critical components of infection prevention. Postoperative wound care and surveillance systems further improved clinical outcomes. Quantitative findings showed reductions in SSI rates ranging from 30–60%, while high compliance with infection control protocols was strongly associated with improved outcomes. However, variability in implementation, compliance, and environmental control measures contributed to inconsistent findings across studies. Conclusion: This review highlights that effective infection control in operating theatres requires a structured, multimodal, and interdisciplinary approach supported by high compliance levels and standardized protocols. Multimodal infection control bundles demonstrated superior effectiveness in reducing surgical site infections and improving perioperative outcomes. The findings emphasize the importance of integrating evidence-based interventions with system-level implementation strategies to enhance surgical safety and patient care.