Defined as the measure of all of an individual’s exposures in a lifetime and how these affect their health, the exposome can help discover the key exposures responsible for chronic diseases. To aid this discovery, the EU-funded ATHLETE project aims to develop a toolbox of advanced, next-generation exposome tools and a prospective exposome cohort. This will be used to systematically quantify the effects of a wide range of environmental risk factors on mental, cardiometabolic and respiratory health outcomes and associated biological pathways during the first 20 years of life. The project’s achievements will aid in the implementation of acceptable and feasible exposome interventions; moreover, they could inform policy recommendations and prevention strategies.