Exposome research has grown considerably in recent years. However, there are areas in which further methodological work or conceptual clarification is needed.
1. What qualifies as exposome research? If we stick to the original definition by Christopher Wild, there are three pillars in the definition: lifelong perspective (starting at conception or even before); the totality of exposures; and complementing external exposure assessment with an “internal exposome” based on biomarkers including omics. As such, exposome research is not feasible. However, it is not clear which (feasible) research would qualify as exposomic. Perhaps two of the criteria might be adopted, where totality can be substituted with multiplicity and interactions.
2. Causality. The typical exposome dataset is characterized by an extremely large number of variables, particularly if omic technologies are included. Apart from the well-known problem of the number of variables that exceeds the number of subjects (that has partial statistical solutions), interpretation is an issue. The typical output is based for example on data reduction and tools like network analysis, that in the best scenario provide molecular pathways that not necessarily are amenable to intervention, i.e. they are not easily actionable; even more so if the concept of network is also applied to outcomes. In one exposure-one disease research the result was reasonably clear and driven by actionability.
3. There is much confusion around the use of exposome research for primary prevention. The terms “precision prevention” or “precision public health” are now frequently used in association with exposomics, but they may be inappropriate (e.g. the proposal of measuring an “expotype”). It can be argued that the added value of the expotype may be limited, for example if measured through the NNT (Number Needed to Treat). Also, public health is largely a matter of structural interventions at the societal level, like taxation, and not only of individual responsibility. Some of the main successes in tackling diseases have been tobacco taxation, sugar taxes and vaccination, rather than individualized health promotion. Population-based prevention is cheaper, it usually addresses several diseases with a single intervention (e.g. smoking or air pollution) and does not need to be replicated at each generation like cure.
 4. The environmental polycrisis. While the immediate health impacts of climate change—such as heat-related mortality or respiratory illness from wildfire smoke—are increasingly recognized, the long-term and cumulative effects of climate change and its related environmental crises (such as biodiversity loss and ecosystem disruption) are much less understood. The exposome framework and omics technologies offer promising avenues to explore the biological consequences of sustained or repeated climate-related exposures. For example, chronic exposure to high temperatures may alter stress hormone regulation or induce epigenetic modifications with long-term effects on cardiovascular, metabolic health or cancer. ?