Efficient water and nitrogen (N) management is critical for sustainable lettuce production in arid regions. This study evaluated N and water management practices for drip-irrigated desert lettuce over three growing seasons at the University of California Desert Research and Extension Center. Two irrigation levels and three N application rates were tested in 1 m and 2 m wide bed configurations. The CropManage (CM) decision support tool was used to estimate crop water requirements for a 100% evapotranspiration (ET) irrigation treatment and to determine the 100% N rate, with additional treatments at 125% ET and 80-120% of the CM-recommended N rate. CM was also used to verify water and N applications in eight commercial fields. Water levels, N rates, and their interaction had no significant effect on yields, whereas 2 m wide beds produced significantly higher yields than 1 m wide beds (p < 0.05). Higher N rates increased N uptake at harvest and significantly reduced N use efficiency (NUE), while higher water levels reduced water use efficiency (WUE) (p < 0.05). Lettuce N uptake increased linearly from thinning to harvest at an average rate of 2.9 kg ha(-1) d(-1). Across commercial sites, CM-recommended applications were lower than farmer standard practice, reducing irrigation by 34% (from 364 mm to 239 mm) and N inputs by 29% (from 202 kg ha(-1) to 144 kg ha(-1)). These findings provide refined N-uptake estimates and highlight opportunities to optimize water and N management, positioning CM as a practical decision-support tool for desert lettuce production.