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The energy transition and global petrochemical market are striking factors reshaping the view of a future refinery. Traditionally known as major producer of fuel to power energy machinery and transport vehicles, today’s refineries are refocusing their technologies toward maximum production of petrochemicals. The major drivers for this restructuring are economic and environmental factors, which are the primary sources of uncertainty in future fuel demand. In this Highlight, the challenges and opportunities that await future refineries are discussed. Future refineries must rethink crude oil processing, and it is worth mentioning that many conventional refineries have already been integrated with petrochemical plants. New technologies for the direct conversion of crude oil to chemicals are being publicized, with some of them reaching commercialization level. To drastically reduce greenhouse gas emissions, refineries need to implement renewable energy sources, process automation, low-carbon hydrogen, and carbon capture, utilization, and storage (CCUS) along with refinery waste recycling. Despite advancements in implementing these new refinery configurations, challenges remain in developing new catalyst formulations for the direct conversion of crude oil to chemicals (COTC) as well as in addressing infrastructure demands for safely transporting and stationing renewable energy sources. The future of the refining industry will increasingly depend on its ability to transition from a fuel provider to an integrated fuel and chemical producer. The successful integration of AI-driven optimization, waste conversion and coprocessing, CCUS, and next-generation COTC catalysts will be key elements of the emerging era of industrial decarbonization.