Developmental age is particularly vulnerable to impacts of environmental exposures. Until recent years, the field of environment and child health has predominantly relied on the study of single exposure–health effect relationships. The exposome is an emerging concept in epidemiology, encompassing the totality of the exposures experienced by an individual throughout life and their changes over time. This innovative approach provides a risk profile instead of individual predictors. Exposome research may contribute to better understand the complex relationships between environmental exposures and childhood respiratory health, in order to implement prevention strategies and mitigate adverse health outcomes across the life span. Indeed, an accurate assessment of the exposome needs several measurements as well as different technologies. High-throughput “omics” technologies may be promising tools to integrate a wide range of exposures. However, analyzing large and complex datasets requires the development of advanced statistical tools. This narrative review summarizes the current knowledge on exposome-based approaches in pediatric respiratory health. Further, it explores practical implementation, associated evidence gaps, research limitations and future research perspectives.