Climate change will substantially exacerbate extreme temperature and heatwaves. The impacts will be more intense across the Middle East and North Africa (MENA), a region mostly characterized by hot and arid climate, already intolerable for human beings in many parts. In this study, daily climate data from 17 fine-resolution Regional Climate Models (RCMs) are acquired to calculate wet-bulb temperature and investigate the mortality risk for people aged over 65years caused by excessive heat stress across the MENA region. Spatially adaptive temperature thresholds are implemented for quantifying the mortality risk, and the analysis is conducted for the historical period of 1951-2005 and two future scenarios of RCP4.5 and RCP8.5 during the 2006-2100 period. Results show that the mortality risk will increase in distant future to 8-20 times higher than that of the historical period if no climate change mitigation is implemented. The coastal regions of the Red sea, Persian Gulf, and Mediterranean Sea indicate substantial increase in mortality risk. Nonetheless, the risk ratio will be limited to 3-7 times if global warming is limited to 2 degrees C. Climate change planning and adaptation is imperative for mitigating heat-related mortality risk across the region.