Extreme heat and wildland fires are identified as key climate risks in Europe. The two risks are interlinked, as the risk of wildland fires increases during periods of extreme heat and decreasing precipitation. Extreme heat increases the death and disease rates for cardiopulmonary disease (CPD). Wildland fires cause intense air pollution in the form of fine particulate matter (PM2.5) and ozone (O3). These are the two major air pollutants threatening human health in Europe, and their main health effects are related to CPD. Episodes of extreme temperatures and extreme levels of PM2.5 and O3 are likely to occur simultaneously and could occur more often, last longer, and become more intense in a warming world. EXHAUSTION will establish exposure projections for extreme heat and air pollution based on the most updated and advanced climate modeling efforts. EXHAUSTION has access to unique retrospective health registries on CPD mortality and morbidity in Northern, Central, and Southern European settings. In addition, EXHAUSTION draws upon a large time-series data base in a multi-country observational study. These data enable us to derive novel exposure-response relationships for heat, air pollution, and CPD. By combining the exposure projections and the exposure-response relationships, EXHAUSTION quantifies the future exacerbation of CPD in European settings and attributes the change in CPD mortality to a changing climate. EXHAUSTION will develop innovative adaptation strategies informed by epidemiological evidence, and address major inequity issues by identifying how age, sex, and indicators of socio-economic status (SES) predict probability for CPD caused by extreme heat and air pollution. EXHAUSTION will model socio-economic cost estimates for the response in CPD, and identify and validate possible adaptation strategies. Cost estimates, including projected health co-benefits of future adaptive measures and greenhouse gas (GHG) mitigation measures will be established.