Belgian and European citizens are exposed to multiple environmental stressors, such as chemicals pollution, noise or lack of green space. The actual PFAS crisis in Flanders illustrates the urgent need for scientific evidence to shape environment & health policy making. EIRENE-Flanders is the Belgian hub of EIRENE RI, the European Environmental Exposure Assessment Research Infrastructure. In line with the holistic ‘exposome’ approach, it will allow to capture the complex interactions between environmental exposure, lifestyle and socio-economic variables, their impact on biological processes in the human body and effects on human health. It provides the infrastructure for large scale collection of human samples and data, efficient measurements of large sets of chemicals, metabolites and proteins, connection to existing datasets, and use of advanced bioinformatics and data science methods to process these large amounts of data. EIRENE-Flanders will contribute to reduce the environmental burden of disease through scientific evidence for environmental, chemicals, food safety and preventive health policies both at Flemish and at European level, and personalised medicine approaches.