An accurate assessment of pollutants’ exposure and precise evaluation of the clinical outcomes pose two major challenges to the contemporary environmental health research. The common methods for exposure assessment are based on residential addresses and are prone to many biases. Pollution levels are defined based on monitoring stations that are sparsely distributed and frequently distanced far from residential addresses. In addition, the degree of an association between outdoor and indoor air pollution levels is not fully elucidated, making the exposure assessment all the more inaccurate. Clinical outcomes’ assessment, on the other hand, mostly relies on the access to medical records from hospital admissions and outpatients’ visits in clinics. This method differentiates by health care seeking behavior and is therefore, problematic in evaluation of an onset, duration, and severity of an outcome. In the current paper, we review a number of novel solutions aimed to mitigate the aforementioned biases. First, a hybrid satellite-based modeling approach provides daily continuous spatiotemporal estimations with improved spatial resolution of 1 × 1 km2 and 200 × 200 m2 grid, and thus allows a more accurate exposure assessment. Utilizing low-cost air pollution sensors allowing a direct measurement of indoor air pollution levels can further validate these models. Furthermore, the real temporal-spatial activity can be assessed by GPS tracking devices within the individuals’ smartphones. A widespread use of smart devices can help with obtaining objective measurements of some of the clinical outcomes such as vital signs and glucose levels. Finally, human biomonitoring can be efficiently done at a population level, providing accurate estimates of in-vivo absorbed pollutants and allowing for the evaluation of body responses, by biomarkers examination. We suggest that the adoption of these novel methods will change the research paradigm heavily relying on ecological methodology and support development of the new clinical practices preventing adverse environmental effects on human health.