The ambition of the SIRENE (Services for envIRonmental Exposure and health assessmeNt in Europe) project is to increase the problem-solving capacity of European society in the Environmental and Public Health and improve capabilities to find and understand disease causations not explained by genetics. While the One Health framework is increasingly recognised as a critical approach to addressing planetary health risks, its practical implementation is limited by disciplinary silos. The exposome concept promoting holistic characterization of the non-genetic factors that influence phenotype and health over the life course offers a unifying scientific framework to address this gap. It represents a transformative paradigm for health research as it goes beyond traditional risk assessment by incorporating multi-domain high-resolution longitudinal data, making the exposome concept particularly well-suited framework for precision public health and prevention strategies. This integrative approach promotes the interdisciplinary evaluation of a wide array of factors originating from natural, built-in, and social environments, occupation, lifestyle, and diet, which can be measured both outside, and in the human body, and encourages environmental, clinical and social scientists to deliver a systematic and comprehensive mapping of these factors, together with associated biological responses, to understand their contributions to disease risks. The SIRENE project brings together 11 ESFRI landmarks and projects to enable challenge-driven research linking environmental factors to human health and advance frontier knowledge and innovation in human exposome by providing open access to complementary high-end infrastructures, integrated services and harmonised data.