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Anthropogenic global change alters the activity and functional composition of soil communities that are responsible for crucial ecosystem functions and services. Two of the most pervasive global change drivers are drought and nutrient enrichment. However, the responses of soil organisms to interacting global change drivers remain widely unknown. We tested the interactive effects of extreme drought and fertilization on soil biota ranging from microbes to invertebrates across seasons. We expected drought to reduce the activity of soil organisms and fertilization to induce positive bottom-up effects via increased plant productivity. Furthermore, we hypothesized fertilization to reinforce drought effects through enhanced plant growth, resulting in even drier soil conditions. Our results revealed that drought had detrimental effects on soil invertebrate feeding activity and simplified nematode community structure, whereas soil microbial activity and biomass were unaffected. Microbial biomass increased in response to fertilization, whereas invertebrate feeding activity substantially declined. Notably, these effects were consistent across seasons. The dissimilar responses suggest that soil biota differ vastly in their vulnerability to global change drivers. Thus, important ecosystem processes like decomposition and nutrient cycling, which are driven by the interdependent activity of soil microorganisms and invertebrates, may be disrupted under future conditions.