Abstract The International Health Regulations (IHR) govern how 196 countries and the World Health Organization (WHO) collectively manage global disease spread while preserving international travel and commercial trade. The COVID-19 pandemic set an unprecedented challenge to the IHR commitments. To address this gap, two scoping reviews were conducted: one identifying global challenges in IHR implementation and the other analyzing challenges, successes and limitations of the IHR during the COVID-19 pandemic. The scoping reviews followed Arksey and O’Malley’s framework and PRISMA methodology, utilizing the PubMed, Medline, World of Science, SCOPUS, and Google Scholar databases, plus backwards citation chaining. Data selection and analysis were guided by pretest forms. From 128 articles screened, 52 met inclusion criteria for the IHR implementation review. 135 challenges were identified, in these categories: (1) requirement of financial and technical resources, (2) lack of enforcement and accountability mechanisms, (3) need for rules clarification, (4) deterrents to reporting, (5) inadequate governance, (6) insufficient cooperation between countries, (7) sovereignty issues, (8) scarcity of guidance and technical support from WHO, (9) lack of inclusion of roles for relevant non-state actors, (10) conflicts and emergencies. In the COVID-19 review, 15 articles were included. Although the role of the IHR during Health Emergencies was acknowledged, most countries faced limitations in its implementation during the pandemic. Key lessons included reinforcing the global health security strategy, reviewing the IHR to address current challenges and strengthening countries and states’ commitment to resolutions compliance. The ongoing debate over IHR updates confirms the need for its revision to safeguard global health. A more effective response grounded on the IHR is needed to face upcoming and expected events of COVID-19’s magnitude and severity.