We find that elevated greenhouse gas concentrations dramatically increase heat stress risk in the Mediterranean region, with the occurrence of hot extremes increasing by 200 to 500% throughout the region. This heat stress intensification is due to preferential warming of the hot tail of the daily temperature distribution, with 95th percentile maximum and minimum temperature magnitude increasing more than 75th percentile magnitude. This preferential warming of the hot tail is dictated in large part by a surface moisture feedback, with areas of greatest warm-season drying showing the greatest increases in hot temperature extremes. Fine-scale topographic and humidity effects help to further dictate the spatial variability of the heat stress response, with increases in dangerous Heat Index magnified in coastal areas. Further, emissions deceleration substantially mitigates heat stress intensification throughout the Mediterranean region, implying that emissions reductions could reduce the risk of increased heat stress in the coming decades.