<p>A warming climate is expected to significantly increase heat-related mortality across Europe, with notable differences between urban and nonurban areas, as well as among regions. In this modelling study, we projected daily mortality from January 1, 2015, to December 31, 2050, under four climate change scenarios (Shared Socioeconomic Pathways [SSP] SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). Projections utilized localized, age- and region-specific exposure-response functions and high-resolution temperature projections statistically downscaled from three global-scale general circulation models to address regional variability and uncertainties. Our results indicate a three-fold increase in the mean heat-related mortality rate by 2040–2050 compared to the 2015–2030 baseline, with annual excess deaths ranging from 3 to 35 per 100,000 people under SSP1-2.6 to 9 to 46 per 100,000 under SSP5-8.5, depending on the region. Southern Europe is projected to experience the largest increases, particularly under high-emission scenarios (SSP3-7.0 and SSP5-8.5), while Western Europe shows a more stable trend. Sustainability scenarios (SSP1-2.6) yield moderate increases, underscoring the potential benefits of low-carbon development pathways. Uncertainty in heat-related mortality projections was largely driven by variations across climate models, emphasising the need for robust climate adaptation and mitigation strategies tailored to regional and demographic vulnerabilities. Targeted interventions, particularly in Southern Europe, are critical to reducing the disproportionate impact of warming temperatures on population health.</p> Graphical Abstract <p></p>