Introduction: Studies have consistently shown that certain categories of healthcare workers, such as those involved in invasive procedures or with direct patient contact, are at heightened risk. This systematic review aimed to comprehensively examine the prevalence, risk factors, and management strategies pertaining to blood-borne infections among healthcare workers. Methods: For this systematic review, a comprehensive search strategy was devised to identify relevant interventional studies addressing blood-borne infections among healthcare workers. The search was conducted across multiple electronic databases, including PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library. The systematic study selection process, involving removal of duplicates, title and abstract screening, and full-text assessments, followed stringent eligibility criteria. Manual searches, expert consultations, and a methodologically sound approach. Results: The systematic review comprised nine interventional studies and clinical trials, with sample sizes ranging from 150 to over 500 healthcare workers. Interventions such as vaccination campaigns against hepatitis B virus (HBV) and implementation of standard precautions yielded significant risk reductions, with HBV vaccination resulting in a 65% decrease in infection risk (RR: 0.35, 95% CI 0.20-0.62) and standard precautions leading to a 58% reduction in occupational exposure risk (RR: 0.42, 95% CI 0.29-0.61). However, educational interventions targeting infection control practices did not significantly alter infection rates (RR: 0.92, 95% CI 0.75-1.12). Conclusions: The findings of this systematic review contribute to the growing body of evidence supporting the effectiveness of various interventions in reducing the risk of blood-borne infections among healthcare workers. While vaccination campaigns and the implementation of standard precautions have consistently demonstrated significant risk reductions, the effectiveness of educational interventions remains variable.