The International Health Regulations (IHR 2005) represent a legally binding framework designed to ensure global health security by requiring Member States to detect, assess, report, and respond to public health emergencies. However, the efficacy of this framework is fundamentally dependent on the awareness, knowledge, and applied competency of healthcare professionals across diverse sectors. This systematic review synthesizes recent literature (2020–2026) to evaluate the current state of IHR 2005 proficiency among healthcare workers globally. Findings indicate a significant "implementation gap": while general awareness of  IHR 2005 has increased following the COVID-19 pandemic, deep technical knowledge and applied competency remain suboptimal, particularly in resource-limited settings and at ground border crossings. Key predictors of competency include professional qualification, years of experience, and participation in specialized training programs like Field Epidemiology Training Programs (FETPs). The review concludes that integrating IHR 2005 standards into national health policies and medical curricula is essential for bridging the gap between global policy and frontline practice.