Background: In today's world, due to intense competition and the rapid pace of production, exploiting knowledge and converting it into economic returns has become a critical management issue for academics and capital owners. Commercialization activities can impact the educational and research programs of universities, potentially leading to resistance against them. Objectives: The current study was conducted to identify the challenges of the Commercialization process in health science research. Methods: This qualitative study was conducted between June and December 2022 in Tehran province, Iran. Data were collected using semi-structured interviews with 22 key individuals, including university management and technology experts, as well as CEOs and experts from knowledge-based companies, selected through purposive sampling. The interview guide was designed based on four in-depth interviews, theoretical foundations, and comparative study findings. The obtained data were analyzed using the conventional content analysis method in MAXQDA 10 software. results: The challenges of the Commercialization process for health sciences research results were categorized into six main themes and 16 sub-themes. The main themes identified in this study were rules and regulations, societal culture, university management and infrastructure, human resources, financial systems, and organizational cooperation with industry. Conclusions: Policymakers, especially senior health managers, can create a suitable platform for the optimal use of resources and the expansion of targeted relationships between universities and industries by incorporating economic insight into academic services. By compiling relevant laws and guidelines, optimizing resource management, achieving financial independence for universities, and increasing the productivity of health research, the high costs associated with the Commercialization of academic research projects can be reduced.