A review of bodies referred to the forensic medicine of Isfahan province over a six-year period highlights the dimensions of the fatal poisoning crisis. During this period, 3,568 poisoning deaths were recorded, indicating a multidimensional problem. To address the problem, five policy strategies were designed based on expert analysis, including strengthening the registration and tracking system, implementing harm reduction programs for opioids, defining mental health services in addiction treatment centers, implementing awareness campaigns, and creating economic incentives in high-risk areas. They were examined in terms of implementation requirements, barriers, beneficiaries, and time frame. The analyses showed that a “harm reduction” approach, along with investment in a data recording system, can have a significant impact on mortality rates. This process faces cultural barriers and cross-sectoral coordination, which can be implemented and evaluated by planning in more critical counties. Based on the effectiveness of the results, the measures can be expanded to other areas and centers and be subject to a continuous evaluation and feedback process. In this way, the imposition of higher human and economic costs can be managed by timely action by health and social policymakers and decision-makers