Nitrogen (N) fertilizer recommendations that match corn (Zea mays L.) N needs maximize grower profits and minimize water quality consequences. However, spatial and temporal variability makes determining future N requirements difficult. Studies have shown no single soil or weather measurement is consistently increases accuracy, especially when applied over a regional scale, in predicting economically optimal N rate (EONR). Basing site N response on soil hydrological group could help account for soil and weather variability and better match in-season corn N fertilization need. Research was conducted across eight Midwestern states totaling 49 different site locations. Sites were delineated into five groups based on USDA-NRCS hydrologic designation and drainage class. Each group was regressed against measured soil and weather variables. Measured soil variables were analyzed by 0 to 0.30 and 0 to 0.60 m depths and included clay content, organic matter, plant available water, and total organic carbon. Measured weather variables, from the time of planting to the time of in-season canopy sensing, included site growing degree days, total precipitation, evenness of rainfall (using the Shannon Diversity Index), and the abundant and well-distributed rainfall. The resulting most significant soil and weather variables for improving EONR estimation were selected to develop an N fertilizer recommendation model for each of the five groups. Model R2 values ranged from 0.48 to 0.85 while root-mean-square errors ranged from 16 to 43 kg N ha-1. When compared to EONR, and considering all five models, 79% of the sites fell within 34 kg N ha-1 of EONR with an R2 of 0.72 and a root-mean-square-error of 34.5 kg N ha-1. Overall, these results suggest that soil hydrological groups can assist in determining which soil and weather interaction will most affect site-specific EONR.