Soil ecotoxicological assays on nanoparticles (NPs) have mainly investigated single components (e.g., plants, fauna, and microbes) within the ecosystem, neglecting possible effects resulting from the disturbance of the interactions between these components. Here, we investigated soil microbial responses to CeO 2 NPs in the presence and absence of earthworms from the perspectives of microbial functions (i.e., enzyme activities), the community structure, and soil metabolite profiles. Exposure to CeO 2 NPs (50, 500 mg/kg) alone decreased the activities of enzymes (i.e., acid protease and acid phosphatase) participating in soil N and P cycles, while the presence of earthworms ameliorated these inhibitory effects. After the CeO 2 NP exposure, the earthworms significantly altered the relative abundance of some microbes associated with the soil N and P cycles (Flavobacterium, Pedobacter, Streptomyces, Bacillus, Bacteroidota, Actinobacteria, and Firmicutes). This was consistent with the pattern found in the significantly changed metabolites which were also involved in the microbial N and P metabolism. Both CeO 2 NPs and earthworms changed the soil bacterial community and soil metabolite profiles. Larger alterations of soil bacteria and metabolites were found under CeO 2 NP exposure with earthworms. Overall, our study indicates that the top-down control of earthworms can drastically modify the microbial responses to CeO 2 NPs from all studied biological aspects. This clearly shows the importance of the holistic consideration of all soil ecological components to assess the environmental risks of NPs to soil health.