<p>Each child’s unique environment and experiences play a crucial role in shaping neurodevelopment and cognitive outcomes. Though a long history of prior research has highlighted the importance of numerous aspects of early life environments, including physical/chemical, psychosocial, socioeconomic, and cultural factors, it remains challenging to fully capture an individual’s complete set of varied exposures, experiences, and external environments (“exposome”) in a single study. The growing field of “exposomics” aims to overcome these challenges by leveraging interdisciplinary ideas and diverse methodologies to assess the additive and interactive effects of multimodal environmental features in relation to health outcomes. Here, we expand upon prior theories to describe a conceptual framework for leveraging exposomics in studies of brain health and cognitive functioning, including the outsized role of environmental influences during sensitive windows of neurodevelopmental plasticity in childhood and adolescence. We also describe current methodologies for the measurement and analysis of the exposome and suggest new ways to apply these methods in future work. Efforts to quantify the exposome in large-scale samples of youth have already begun to yield important new insights regarding environmental impacts on cognitive neurodevelopment and hold great promise for future work aiming to support healthy development in youth.</p>