Iran’s oil refining industry, which serves as the backbone of the national economy and supplies over 95% of domestic transportation fuel requirements, is situated at the intersection of geopolitical challenges, global energy transition dynamics, and increasing environmental pressures. Adopting a foresight studies approach, this research identifies and analyzes the strategic drivers and uncertainties that will influence the design and development of Iran’s petroleum refineries through 2050. Utilizing a mixed-methods methodology encompassing a systematic literature review, analysis of international reports (OPEC, Shell, IEA), macro-level (PESTEL) and micro-level (Porter’s Five Forces) analyses, semi-structured expert interviews, and MICMAC (Matrix of Cross-Impact Multiplications Applied to a Classification) structural analysis, 34 key factors were extracted and ranked. The findings indicate that foreign policy, domestic governance, demographic trends, global energy transition, emerging technologies in the oil, gas, and petrochemical sectors, environmental policies and regulations, and domestic consumption patterns are the eight principal drivers steering the system. Furthermore, the results demonstrate that the confluence of environmental pressures (decarbonization, stringent environmental regulations), shifting demand patterns toward petrochemical products, and restricted access to advanced technologies owing to sanctions reinforces the strategic imperative to transform conventional refineries into integrated “petro-refinery” complexes. This study provides a dynamic roadmap for policymakers and industry leaders to enhance sectoral resilience, decarbonization, and global competitiveness through integrated petro-refineries, novel technologies, and smart governance while capitalizing on opportunities arising from the eastward shift of global energy gravity.