The characteristics of the growing environment (arid and semi-arid regions with abundant light), wastage of water, types of fertilizers used, quality of the plants, and the decline in yield due to the need for large quantities of water and fertilizers are the most significant obstacles to wolfberry cultivation. To cope with the scarcity of water caused by the increase in the area of wolfberry cultivation and to improve the efficiency of the utilization of water and fertilizers, a two-year field experiment was conducted in a typical area of the central dry zone of Ningxia in 2021 and 2022. The effects of different water and nitrogen coupling on the physiology, growth, quality, and yield of wolfberry were investigated, and a water and nitrogen management model with better indicators was constructed based on the TOPSIS model and a comprehensive scoring method. In the experiment, three irrigation quotas of 2,160, 2,565, and 2,970 m3 ha-1 (I1, I2, and I3) and three N applications of 165, 225, and 285 kg ha-1 (N1, N2, and N3) were established; the local conventional management served as the control (CK). The results showed that the growth index of wolfberry was most significantly affected by irrigation, followed by the water and nitrogen interaction effect, and the nitrogen application had the least effect. The growth and development of wolfberry plants mainly takes place during the fruit ripening and flowering periods, and growth almost stops after entering the fruit ripening period. The chlorophyll (SPAD) values were affected by irrigation and nitrogen application to a significant level, except for during the spring tip period, but the effect of water and nitrogen interaction was not significant. The SPAD values of N2 treatment were better under different irrigation. The daily photosynthetic activity of wolfberry leaves peaked between 10:00 am and noon. The daily photosynthetic dynamics of wolfberry were affected by irrigation and nitrogen application to a significant level during the fruit ripening period, and the transpiration rate and leaf water use efficiency were affected by water and nitrogen interaction to a significant level during 8:00 am and noon, while the effect was not significant during the spring tip period. The yield, dry-to-fresh ratio, and 100 grain weight of wolfberry were significantly affected by the irrigation, nitrogen application, and their interaction effects. Specifically, the two-year yield with I2N2 treatment increased by 7.48% and 3.73%, respectively, compared to CK. The quality indices were significantly affected by irrigation and nitrogen application, except for the total sugars; other indexes were also significantly affected by water and nitrogen interaction effects. The evaluation of the TOPSIS model showed that the I3N1 treatment yielded the best quality of wolfberry, and the results of the integrated scoring method based on the growth, physiology, yield, and quality indicators and water-saving objectives showed that the I2N2 (2,565 m3 ha-1, 225 kg ha-1) treatment was the optimal water and nitrogen management mode for drip-irrigated wolfberry. Our findings provide a scientific basis for the optimal irrigation and management of fertilization of wolfberry in arid regions.