Robustness is the measure of the ability to perform well across multiple environments. The genetics of robustness in lettuce (Lactuca sativa L.) under changing nitrogen application was studied by two parameters obtained from linear regression analysis. Robustness in changing water application was assessed by two parameters, relative efficiency component (REC) and susceptibility component (SC). The efficiency, sensitivity, and the effect of reduced irrigation on these parameters was assessed for 50 lines of lettuce in 2011. Efficiency, sensitivity, and plant nitrogen uptake and utilization were important traits in robustness under changing nitrogen application. Eight cultivars were re-evaluated in 2012, 2014, and 2016 under high and low nitrogen treatments in order to estimate the repeatability of efficiency and sensitivity. Repeatability was greater for efficiency than sensitivity. In addition, the genetics of efficiency, sensitivity, REC, SC, nutrient concentration, nutrient content, dry to fresh biomass percentage, bolting, and shoot biomass production were studied by quantitative trait locus (QTL) analysis of a recombinant inbred line population derived from the cultivars Grand Rapids and Iceberg. The population was phenotyped in three experiments and genotyped by sequencing. Major clusters of QTLs for these traits were identified in linkage groups (LGs) 3, 7, and 9. Minor effect QTLs for sensitivity were identified in LGs 3 and 4. Intermediate effect QTLs for SC were identified in LGs 4 and 7. These results provide evidence that the components of robustness under changing nitrogen (efficiency and sensitivity) and water (REC and SC) availability are genetically independent and can be improved through breeding.