OBJECTIVES: This qualitative study aimed to identify the key challenges associated with managing patients affected by biological emergencies in Iran. METHODS: This study was part of grounded theory research using the constant comparative analysis method proposed by Corbin (2014). Data were gathered through semi-structured interviews with 25 individuals with expertise or experience in managing biological emergencies. Purposive sampling, followed by theoretical sampling, was employed until theoretical saturation was reached. Data collection was conducted between April and November 2023, and MAXQDA software (2020) was used for data analysis. RESULTS: After several rounds of data analysis and summarization, considering similarities and differences, four main categories and 14 subcategories were identified. The main categories included: 1) lack of a comprehensive risk communication strategy, 2) inefficiencies in patient flow mismanagement, 3) systemic political and governance challenges, and 4) deficiencies in resource allocation and utilization. CONCLUSION: This study highlighted the challenges faced by Iran's Healthcare system in managing affected individuals in biological emergencies. Key issues included mismanagement of patient flow and systemic inefficiencies. Addressing these challenges is essential for enhancing the effectiveness and sustainability of Iran's Healthcare system. Further research is recommended to provide practical strategies for managing biological emergencies in the future.