Vegetation restoration in metallic tailing reservoirs is imperative to restore the post-mining degraded ecosystems. Extracellular enzymes determine microbial resource acquisition in soils, yet the mechanisms controlling the enzyme activity and stoichiometry during vegetation restoration in metallic tailing reservoirs remain elusive. Here, we investigated the variations and drivers of C-, N- and P-acquiring enzymes together with microbial community along a 50-year vegetation restoration chronosequence in the China's largest vanadium titanomagnetite tailing reservoir. We found a parabolic pattern in the enzyme activity and efficiency along the chronosequence, peaking at the middle restoration stage (similar to 30 years) with approximately six-fold increase relative to the initial 1-year site. The enzyme ratios of C:P and N:P decreased by 33 % and 68 % along the chronosequence, respectively, indicating a higher microbial demand of C and N at the early stage and a higher demand of P at the later stage. Soil nutrients directly determined the enzyme activities and stoichiometry, whereas microbial biomass and community structure regulated the temporal pattern of the enzyme efficiency. Surprisingly, increased heavy metal pollution imposed a positive effect on the enzyme efficiency indirectly by altering microbial community structure. This was evidenced by the increased microbial diversity and the conversion of copiotrophic to oligotrophic and stress-tolerant taxa along the chronosequence. Our findings provide new insights into microbial functioning in soil nutrient dynamics during vegetation restoration under increasing heavy metal pollution.