Regenerative agriculture (RA) is expanding across the Western Canadian Prairies, but its microbial foundations under climatic constraints remain insufficiently integrated. This review synthesizes evidence from long-term prairie field experiments, regional datasets, and global meta-analyses to evaluate how regenerative management reshapes soil biological processes and system performance. Across studies, RA is consistently associated with increases in microbial biomass, enzymatic activity, arbuscular mycorrhizal connectivity, and nitrogen-use efficiency, alongside gains in soil organic carbon, aggregation, and water-holding capacity. These biological enhancements correspond with lower soilborne disease pressure, moderated weed dynamics, reduced dependence on synthetic nitrogen and pesticides, and progressively stabilized yields under semi-arid, short-season conditions. Prairie findings broadly align with global regenerative trends, although short-term and site-specific responses range from negative to positive, underscoring the importance of temporal scale. In regions characterized by high interannual climate variability, conserved microbial mechanisms appear central to resilience, while the rate at which agronomic benefits emerge depends on climatic and edaphic constraints. Overall, the synthesis identifies microbial restoration as the central pathway linking regenerative management to soil health, pest suppression, and sustainable productivity. Continued long-term, system-level research is needed to refine regionally adapted regenerative transitions and to clarify how microbial processes mediate resilience under future climate uncertainty.