Background <p>Health Technology Assessment (HTA) is vital for evidence-based decision-making and efficient resource allocation. Although HTA has gained importance in Iran’s health policy agenda, its development faces major barriers. Among these, conflicts of interest (COI) remain a critical yet understudied challenge that can undermine the integrity of HTA processes. This study explored how COI manifest within Iran’s HTA environment and hinder its development.</p> Methods <p>A qualitative design was used, employing purposive sampling to select key informants involved in HTA and health policymaking. Twenty-eight semi-structured interviews were conducted with policymakers, academics, healthcare professionals, and representatives from regulatory and insurance bodies. Data were analyzed thematically using an inductive approach to identify the types, sources, and impacts of COI.</p> Findings <p>Participants described multiple personal, institutional, and systemic COI influencing HTA. Key themes included the lack of formal disclosure and management mechanisms, strong industry influence, overlapping roles of decision-makers, and weak regulatory oversight. These factors distorted priority-setting, delayed the adoption of cost-effective technologies, and eroded public trust. Cultural norms favoring informal relationships and political patronage further reinforced these problems.</p> Conclusions <p>COI threaten the credibility and transparency of HTA in Iran. Strengthening governance frameworks, ensuring institutional independence, and promoting ethical accountability are essential to enhance HTA integrity. The findings provide insights for other low- and middle-income countries seeking to institutionalize HTA within complex governance systems. This study highlights that managing COI requires not only technical solutions but also interdisciplinary approaches, particularly drawing on legal frameworks and organizational management theories, to address governance failures in Iran’s health system.</p>