This study investigates the structure-performance relationships in different zeolite-solvent systems that are suitable for microwave-assisted dehydration of food waste-derived fructose to 5-hydroxymethylfurfural (HMF). Different types of zeolites (MFI, BEA, and Y) were examined as acid catalysts. Water was first tested as the greenest solvent (baseline), followed by dimethyl sulfoxide (DMSO), acetone, -valerolactone (GVL), and propylene carbonate (PC)/water (1:1 v/v) binary solvent systems. The results showed that the HMF yield was independent of particle size of MFI zeolite in water. The secondary porosities improved the HMF yield, while byproducts formation (via rehydration or polymerization) was also increased due to the enlarged channels in zeolites. All tested zeolites showed higher fructose conversion, HMF yield, and HMF selectivity in organic-water solvent systems than in water. The synergistic effects of the substrates, catalysts, and solvent-product interactions in the hydrophobic Y zeolite/DMSO system yielded the highest fructose conversion (72.4%) and HMF yield (49.2%). This study advances our understanding of green solvents and functionalized zeolites for microwave-assisted biomass conversion in sustainable biorefinery.