Yield and quality improvements in Canada Western Red Spring (CWRS) wheat (Triticum aestivum L.) are increasingly difficult to attain, which behooves a systems approach to unlock genotype (G) × environment (E) × management (M) synergies. This 25 site-year study was designed to assess a G × E × M systems approach to improve CWRS agronomics, quality, and N use efficiency (NUE). The investigation consisted of genetics (AAC Viewfield vs. AC Stettler), N source (untreated urea; urea + urease inhibitor, N-(n-butyl) thiophosphoric triamide (NBPT); urea + nitrification inhibitor, nitrapyrin; urea + dual-inhibitor (NBPT + dicyandiamide); and polymer-coated) and N timing/placement (all-banded at planting, two-split applications and three-split applications), deployed across diverse soil zones in western Canada. Differential yield responses were observed between cultivars as AAC Viewfield produced superior yield over AC Stettler (+4.3%) in black and grey soils, while yield attainment was similar in dark brown soils. Genetic improvement over AC Stettler seemed most apparent in water abundant environments; however, AC Stettler was often superior in drier conditions. All N sources produced comparable outcomes for yield, quality, NUE, and net returns. In black and grey soils, adopting either all-banded or two-splits improved grain yield due to augmented seedling vigor, heads per plant, and N recovery. The timing of split-applications introduces more risk to yield and is likely attributed to a poorly developed source:sink relationship in the critical growth period if applied late to optimize grain protein. This highlights the complexity of the system and balance needed to harness the potential synergy between G, E, and M components.