The worldwide outbreak of the COVID-19 has turned the need to pursue health diplomacy into an undeniable reality in developing countries, especially Iran. Inconsistent, short-term, and intermittent attempts have been made for this purpose in Iran; however, the goals and plans of Iran’s Ministry of Foreign Affairs are not still clear and appraisable. This study aims to determine the requirements and challenges that Iran faces to adopt a kind of successful and efficient diplomacy. In this regard, the research hypothesis emphasizes the role and importance of health diplomacy in Iran’s foreign policy as a requirement to relieve distrust and tension in relations with other countries, something which is considered a challenge. Therefore, a qualitative explanatory-analytical approach was used in this study. Moreover, a desk method was employed to collect the necessary data from two groups of printed and electronic sources in order to purposefully answer the main research question. According to the findings, Iran should consider a series of political and economic requirements in its foreign policy to benefit from a kind of successful health diplomacy. In fact, Iran’s most important requirements were identified as perceiving the importance and position of health diplomacy, formulating strategic plans, training professional diplomats, relieving tensions, and building trust. However, the most prominent international challenges were identified as distrust in Iran, uneasy and tense foreign relations, and the presence of powerful rivals on both regional and international scales. Furthermore, the domestic challenges were classified as content-related, structural, cultural, governance-related, economic, and process-related problems.