Cotton is the main economically important crop in Xinjiang, China, but soil salinization and shortage of water and nutrients have restricted its production. A field experiment was carried out in the salinity-affected arid area of Northwest China from 2018 to 2019 to explore the effects of nitrogen and water regulation on physiological growth, yield, water and nitrogen use efficiencies, and economic benefit of cotton. The salinity levels were 7.7 (SL) and 12.5 dS/m (SM). Drip irrigation was used with low, medium and adequate irrigation levels representing 60%, 80% and 100% of cotton crop water demand, respectively, and three nitrogen applications, i.e., 206, 275 and 343 kg/hm 2 , accounting for 75%, 100% and 125% of local N application, respectively were used. The multi-objective optimization based on spatial analysis showed that, at SL salinity, water use efficiency (WUE), nitrogen use efficiency (NUE), economic benefit and yield simultaneously reached more than 85% of their maxima at 379.18-398.32 mm irrigation and 256.69-308.87 kg/hm 2 . At SM salinity, WUE, yield and economic benefit simultaneously reached more than 85% of their maxima when irrigation was 351.24-376.30 mm and nitrogen application was 230.18-289.89 kg/hm 2 . NUE, yield and economic benefit simultaneously reached their maxima at 428.01-337.72 mm irrigation, and nitrogen application range was 222.14-293.93 kg/hm 2 . The plants at SL salinity had 21.58%-46.59% higher WUE rates, 14.91%-34.35% higher NUE rates and 20.71%-35.34% higher yields than those at SM salinity. The results are of great importance for the nutrient and water management in cotton field in the arid saline area.