Environmental change coupled with alteration in human lifestyles are profoundly impacting the microbial communities that play critical roles in the health of the earth and its inhabitants. To identify bacteria and fungi that are resistant and susceptible to habitat changes respectively, we retrieved paired 16S and ITS rRNA amplicon sequence data from 1,580 host, soil, and aquatic samples and explored the ecological patterns of the thousands of detected bacterial and fungal genera. Through this large-scale analysis, we identified 48 bacterial and 4 fungal genera that were prevalent and abundant across the three biomes, demonstrating their resilience in diverse environmental conditions. These generalists comprised a substantial fraction of the taxonomic diversity of their respective kingdom. Their distribution across samples explained a large percentage of the variation in the cross-kingdom community structure. We also found that the genomes of these generalists were larger and encoded more secondary metabolism and antimicrobial resistance genes, illuminating how they can dominate diverse microbial communities. Conversely, 30 bacterial and 19 fungal genera were only found in a single habitat, suggesting they cannot readily adapt to different and changing environments. These findings can contribute to designing microbiome-mediated strategies for pressing global changes.