Abstract: Achieving global decarbonization is essential to mitigate climate change, yet heat-intensive industries remain challenging to decarbonize through electrification alone. Green hydrogen offers a clean alternative to replace fossil fuels and fossil fuel?based hydrogen, but its deployment requires careful planning and robust economic assessment. This study addresses the optimal design of a green hydrogen supply chain in a Mediterranean region where ceramics and cement dominate as energy-intensive industries, while oil refining is the main consumer of fossil fuel-based hydrogen. The region also faces freshwater scarcity due to its climate and the high demand for water from tourism and agriculture. A Mixed-Integer Linear Programming (MILP) model is developed to minimize the total cost of supplying green hydrogen by determining the optimal size and location of renewable energy sources, integrating desalinated seawater from existing desalination plants as feedstock, and designing the infrastructure connecting production, storage, and demand centers. The cost-optimal configuration includes 3.4 GW of PEM electrolyzers requiring 41.1 m3/h of desalinated seawater supplied by existing desalination plants, along with 5.1 GW of wind and 12 GW of solar power as renewable energy sources for large-scale hydrogen production. Results show that supplying green hydrogen to these industries can avoid approximately 4.4 million tons of CO2 emissions annually, achieving a levelized cost of hydrogen (LCOH) of $2.18/kg for the period 2030?2050. Beyond this case study, the proposed framework provides a replicable methodology for planning hydrogen-based energy systems in regions facing similar water and decarbonization challenges

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