Mortality rates rise during hot weather in England, and projected future increases in heatwave frequency and intensity require the development of heat protection measures such as the adaptation of housing to reduce indoor overheating. We apply a combined building physics and health model to dwellings in the West Midlands, UK, using an English Housing Survey (EHS)-derived stock model. Regional temperature exposures, heat-related mortality risk, and space heating energy consumption were estimated for 2030s, 2050s, and 2080s medium emissions climates prior to and following heat mitigating, energy-efficiency, and occupant behaviour adaptations. Risk variation across adaptations, dwellings, and occupant types were assessed. Indoor temperatures were greatest in converted flats, while heat mortality rates were highest in bungalows due to the occupant age profiles. Full energy efficiency retrofit reduced regional domestic space heating energy use by 26% but increased summertime heat mortality 3–4%, while reduced façade absorptance decreased heat mortality 12–15% but increased energy consumption by 4%. External shutters provided the largest reduction in heat mortality (37–43%), while closed windows caused a large increase in risk (29–64%). Ensuring adequate post-retrofit ventilation, targeted installation of shutters, and ensuring operable windows in dwellings with heat-vulnerable occupants may save energy and significantly reduce heat-related mortality.