Soil enzymes drive organic matter decomposition and nutrient mineralization, playing a pivotal role in plant and microbial nutrient acquisition. Yet, how microenvironmental factors regulate enzyme activities during the early spring snowmelt period in the Gurbantunggut Desert remains poorly understood. To address this, we collected soil samples from three slope positions (bottom, middle, and top of sand dunes) over a two-week period during the snowmelt season in 2019. We analyzed soil physicochemical properties and measured the activities of eight enzymes involved in carbon (C), nitrogen (N), and phosphorus (P) cycling:alpha-1,4-glucosidase, beta-1,4-glucosidase, beta-D-cellobiohydrolase, beta-1,4-xylosidase, urease, N-acetyl-beta-D-aminoglucosidase, leucine aminopeptidase, and alkaline phosphatase. Our findings revealed that soil water content (SWC) was identified as the primary driver of soil enzyme activity variation during the snowmelt period, explaining >50% of the total variance in redundancy analysis. Significant spatiotemporal variations in both soil properties and enzyme activities were observed. Overall, activities of C-, N-, and P-acquiring enzymes increased over the sampling period and exhibited topographic gradient, with the highest values predominantly at dune tops and lowest at dune bottoms. Structural equation modeling (SEM) elucidated that slope position exerted contrasting effects: it directly and indirectly inhibited C-acquiring enzyme activities, but promoted those related to N and P acquisition. In contrast, both SWC and aboveground biomass (AGB) negatively influenced all enzyme groups, likely due to nutrient leaching following large water pulses and reduced litter inputs from lower AGB, respectively. Beyond these primary controls, soil organic carbon, available nitrogen and the C/N ratio also contributed to regulating enzyme activities. These findings underscore the complex interplay between enzyme activities and biotic/abiotic factors, emphasizing the role of micro-topography in mediating nutrient cycling during a hydrologically transient phase in arid dryland ecosystems.