The exposome concept was introduced by Christopher Wild, a molecular epidemiologist, in 2005. He defined it as the totality of life-course environmental exposures (including lifestyle factors) from the prenatal period onwards. The concept has attracted widespread attention since 2010 and is now an important political and financial driver of research into environmental health. But this ambitious holistic approach to human health exposures raises several methodological and conceptual challenges. If the multiple promises of exposome research seem to have in common the promotion of a holistic and integrative approach to environmental health, the meaning given to this holism, and the integrative and interdisciplinary approach associated with it, varies from one researcher to another, usually according to their disciplinary specialization. In fact, in the background of these variations, there remain at least three main aspects of the exposome that need to be clarified. They concern the scope (should social data be included?), the nature and degree (reductive unification, integrative pluralism, or interactive pluralism?), and the object (data? explanations? methods?) of the integration of exposures that is to be achieved via the exposome approach.