The COVID-19 pandemic has underscored the importance of the International Health Regulations (IHR) (2005) in addressing global health emergencies. This review aims to improve healthcare system capabilities, future preparedness, and actions in the Eastern Mediterranean Region, particularly in low-resource areas. The IHR, established in 1969, initially focused on 6 diseases but has since expanded to include a wider range of public health threats. These regulations establish a globally recognized legal framework that is applicable to all 196 states parties, including all 194 World Health Organization member states. The IHR prioritize the prevention, protection, and control of global disease transmission while minimizing unwarranted disruptions to international travel and commerce. Nonetheless, the response to COVID-19 in the Eastern Mediterranean Region revealed a range of deficiencies despite the regulatory strengths. Some countries encountered challenges in fully complying with their IHR obligations, particularly in terms of preparedness, and occasional geopolitical tensions obstructed international collaboration. The pandemic experience underscores the need for improved trust, resource allocation, and regulatory revisions to address upcoming global health challenges. This case study highlights positive aspects of the pandemic response, including the swift exchange of information and global cooperation, while also recognizing shortcomings, such as delays in reporting and unequal vaccine access. In summary, the COVID-19 pandemic underscores the urgency of subsequent updates to the IHR or comparable accords, such as the IHR amendments and the pandemic treaty, to rectify these deficiencies. Updates should place a greater emphasis on transparency, cultivating trust, enhancing preparedness, and establishing mechanisms that incentivize comprehensive compliance among all participating nations.