As one of the largest industrial emitters, today's refineries must take action to reduce emissions in response to global climate change and net -zero targets. However, the decarbonization of refineries is complex due to the diverse range of processes involved, high energy requirements, and the limited availability of cost-effective clean alternatives. In this study, a holistic approach is proposed for refinery decarbonization based on atomic, energy, and exergy flow analysis by characterizing feedstocks and products using their stoichiometric formulas (CH j O k N m S n ) and thermodynamic properties. Applied to the Blueprint model, representing a typical European refinery, it is revealed that 2.4% and 1.3% of carbon emissions stem from the exit of oxygen atoms during combustion and hydrogen production, accounting for 4.3% of total energy input. Decarbonization options for future refineries such as product portfolio changes and alternative feedstocks were further explored. While maximizing naphtha for chemicals leads to increased CO 2 emissions due to higher hydrogen-to-carbon ratios in products, biomass with electrolysis emerges as a preferable option for its low carbon losses and high exergy efficiency. The thermodynamic analysis of this study can provide valuable insights and theoretical instructions to industrial operators into the transition to future refineries.