As the concept of exposome is nowadays emphasized for its integrative virtues, this holistic vision of pathogenesis was already shared by some illustrious and ancient figures of medicine. The question is not so much whether this holistic and integrative vision of the exposome represents a real novelty in the field of environmental health studies, but rather to determine the extent to which this concept and the techniques associated with it are really contributing to the set up of a more integrative and holistic knowledge of the environmental determinants of health. In this chapter, we propose to go back over the epistemological and methodological paths in the study of spatial dimension of health. With regards to these historical and scientific contexts, the exposome seems to extend a holistic and integrative scientific dynamic that already exists, for various reasons, in the field of spatial analyses in health. The development of exposomic studies represents a significant opportunity for better integration of environmental measures into health studies with high level of precision, thanks to molecular data. But the exhaustive measure of environmental factors potentially contributing to health status and inequalities is still limited by technical and financial constraints which questions the representativeness of the studies and their ability to address all public health issues, usually reported by studies in epidemiology and health geography. This should lead us to qualify not the scientific interest of the exposome but its claim to provide objective knowledge to support policies addressing public health issues, such as socio-spatial inequalities in health.