According to estimates from the World Health Organization (WHO), organophosphate pesticides are responsible for approximately 300,000 deaths worldwide. In the United States, documented cases of organophosphate pesticide exposure number around 8000, with a small number of fatalities occurring annually. The health risks associated with these pesticides affect those living in agricultural areas, as well as farmers and pesticide applicators. Despite the intervention of government agencies in Illinois to regulate pesticide application, studies have shown that these pesticides remain present in the soil, crops, water, and air. Urban–agricultural interface communities around Sangamon County exhibit significant levels of air pollution due to pesticide spray drift, although the lack of reliable pesticide data poses a challenge in estimating the extent of the problem. Therefore, developing novel strategies to reduce the impact of pesticides on environmental health is a critical and effective research area. Currently, new, dependable models and methods are being developed to calculate spray drift and mitigate its effects. The primary objective of this study was to investigate whether and to what extent organophosphate pesticide spray drifts into urban–agricultural interface communities in Sangamon County, Illinois. To achieve this, the current study employed an integrated approach that combined the capabilities of the HYSPLIT and AgDRIFT models to evaluate organophosphate pesticide spray drifting at both the field- and county-level scales. In the absence of precise pesticide quantity data, this novel approach allowed for field simulations within identified exposure drift zones. The preliminary findings indicate that all residential areas close to agricultural areas are at risk of pesticide drift, as buffer zones do not exceed 25 m. Furthermore, of the 34 water bodies (rivers, lakes, streams, and drains) in the 30,200-acre study region, 12 are within the high-drift zone for pesticide spray drift from corn and soybean fields. Finally, the potential for organophosphate pesticide drift was present in approximately 106 buildings, covering an area of 10,300 km2.