EIRENE RI is pioneering the first European distributed research infrastructure focusing on the human exposome by bringing together more than 50 institutions from 20 European countries and the USA. EIRENE brings the complementary capacities available in Member States and harmonizes and upgrades them to effectively address current scientific and societal challenges in the environment and health domains. The exposome measures the environmental exposures (i.e., non-genetic factors) encountered by individuals to understand their impacts on phenotype and health. It considers the various sources of exposure, such as diet, lifestyle, and the environment. It can be measured in the environment (external component of the exposome) and the body (internal component of the exposome). Exposome-driven approaches go beyond the standard environmental health approaches, promoting the discovery of unforeseen links between stressors and impacts. They consider an individual's life course, community, and ecosystem. However, existing methodologies fall short, highlighting the need to develop new analytical capacities and computational tools for analyzing large datasets. The research findings will help elucidate the non-genetic factors behind the development of chronic conditions, thereby improving the health of citizens. EIRENE's mission to develop and operate a research infrastructure in the exposome field is unique in Europe. The exposome concept is also gaining increased awareness and interest within European agencies, such as EFSA, EchA, EEA, JRC, and national agencies. Specifically, EU and MS agencies are deliberating on integrating exposome considerations into regulatory decisions. EIRENE works closely with the European Partnership for Assessment of the Risk of Chemicals (PARC). PARC conducts environmental and human biomonitoring across Europe, poised to leverage EIRENE's analytical capacities. EIRENE collaborates closely with European research clusters, notably the European Human Exposome Network (EHEN). EHEN projects explore the health ramifications of urbanization, working life, child development, mental health, immunity, and respiratory diseases. They also develop tools and informatics platforms for analyzing vast datasets on environmental exposures and their health impacts. EIRENE also cooperates with the International Human Exposome Network (IHEN), a project to enhance global research and cooperation on the exposome. The partnerships, clusters, and projects mentioned above generate substantial volumes of data and contribute to advancing toolboxes and methodologies. Nonetheless, given their finite duration, EIRENE emerges as a highly viable solution for ensuring the sustainability of their activities after they end. The specific objectives of EIRENE are to 1) Measure and Model the Exposome by assessing its components and performing toxicokinetic modeling to understand exposure dynamics; 2) Assess Biological Effects and Health Impacts by utilizing methodologies such as toxicology and New Approach Methodologies (NAMs), population studies and cohorts; 3) Ensure Cohorts Sustainability; 4) Develop Data Storage, Management, and Computational Platforms.