Newly registered Canadian Western Red Spring (CWRS) wheat cultivars are becoming increasingly high yielding with field yields greater than 6.7 t ha-1being reported by some growers. With these new high yielding genetics, growers in highly productive areas of western Canada have the opportunity to intensify their agronomic management of CWRS wheat with high levels of nitrogen (N) fertilizer and fungicide applications. Small plot field trials were conducted in three site-years to test increasing N fertilizer rates (from 0 to 225 kg N ha-1), urea/ESN blends, and multiple fungicide applications on new CWRS wheat cultivars, AAC Brandon and AAC Viewfield. The objective is to optimize agronomic performance, yield, protein, test weight and economic returns. As expected, yields increased as N fertilizer rate increased but economic N fertilizer rates varied depending on the growing environment. AAC Viewfield required an additional 45 kg actual N ha1 to meet 13.5% protein compared to AAC Brandon. Inclusion of ESN did not improve yield or protein content of the harvested grain compared to urea alone. The yield response to prothioconazole and tebuconazole at BBCH 61-63 increased yields between -1.2 to 19.9% depending on environmental conditions and disease pressure. Yields of AAC Viewfield were 5.0% higher than AAC Brandon at 100 kg N ha-1 but 6.1% higher than AAC Brandon at 150 kg N ha-1. Both yield and protein data suggest that AAC Viewfield is better suited to high input N management compared to AAC Brandon. This research provides evidence for the need to couple GxM components with environmental conditions to enhance the global sustainability of wheat production.