Introduction: Nosocomial infections remain a significant threat to patient safety worldwide, driving morbidity, mortality, and escalating healthcare costs. Despite comprehensive guidelines from the WHO, CDC, and ECDC, variability in recommendations and persistent implementation gaps impede optimal uptake. Objective: To critically assess current international and regional standards for preventing and controlling healthcare‐associated infections (HAIs) and to propose feasible, context‐specific strategies for local implementation that empower healthcare professionals to reduce infection rates meaningfully. Material and Methods: We conducted a systematic review of key HAI prevention and management guidelines published between 2013 and 2023. The methodological quality of each document was evaluated using the AGREE II instrument. Results: All guidelines converge on essential measures: rigorous hand hygiene, standardized environmental disinfection protocols, and robust antimicrobial stewardship programs. However, antibiotic regimens for routine HAIs (e.g., catheter‐associated urinary tract infections) differ markedly, and few guidelines offer clear pathways for implementation in facilities constrained by staffing, equipment, or medication shortages. Interviewees cited critical challenges, including insufficient staffing levels, inconsistent training quality, limited diagnostic capacity, and underdeveloped surveillance systems. Conclusions: Harmonization of core recommendations is needed to reduce clinician confusion. We propose a practical implementation framework. Tailoring global best practices to local realities promises improved compliance, optimized resource use, and a significant reduction in nosocomial infection burden.