Aims Soil microbes play critical roles in regulating the turnover of soil organic carbon (SOC) and nutrients, and microbial metabolic limitation should draw more attention in desert ecosystems. However, soil extracellular enzymes activity (EEA) response and microbial metabolic limitation to atmospheric N deposition and increased precipitation in desert-shrubland are still poorly understood. Methods The study examined the effects of long-term (9 year) N and water additions (i.e., 5 g N m−2 yr−1, 30% ambient precipitation increase and their combination) on EEAs and soil microbial resource limitation, as well as explored their controlling factors in the Gurbantunggut Desert in northwestern China. Results The results showed that N and water additions significantly enhanced soil EEAs and considerably aggravated microbial phosphorous (P) limitation. Water addition and the N-water combination addition alleviated carbon (C) limitation, but N addition alone strengthened microbial C limitation. The interaction of N and water additions relieved the negative impact of N addition on soil microbial C limitation, and positively aggravated microbial P limitation. Soil microbial C limitation was primarily driven by soil moisture and organic C concentration, while the soil microbial N/P limitation was chiefly controlled by soil water and available P contents. Conclusions The influences of either N- or water addition alone on desert ecosystem biogeochemical processes may be altered by their concurrent occurrence. Overall, these findings highlight water availability is more effective at modifying microbial metabolisms than N accumulation in desert ecosystems. Altogether, this may help to predict how terrestrial C and nutrient flow could be induced by global change factors..