Microbial degradation of organic pollutants is crucial to mitigate environmental risks to wildlife and humans. This capacity hinges on factors such as microbial community composition, environmental conditions, pollutant characteristics, and the presence of metals/metalloids, surfactants, or co-metabolites. Our meta-analyses, covering 3095 data pairs across 158 microbial species and 148 pollutants, offer insights into the factors regulating microbial degradation of organic pollutants in sterilized mediums. Degradation rates were dependent on the compounds: hormones degrade fastest, largely by Basidiomycota fungi. Microbial monocultures have superior overall degradation capacity (+35%·day−1) compared to mixed co-cultures (+8%·day−1), particularly because monocultures have a 3.6 times faster initial 5-day degradation rate. Fungal monocultures demonstrate greater resilience to additional compounds (i.e., metals/metalloids, co-metabolites, surfactants) than bacterial monocultures, attributed to their broader enzymatic and metabolic capabilities. Degradation rates of organic pollutants under aerobic conditions are sevenfold faster than in anoxic environments, as oxygen is the strongest electron acceptor, boosting energy production for microorganisms. Metals/metalloids generally reduce microbial degradation efficiency (−21%), primarily by reducing oxidoreductase activities (−54%). Surfactants accelerate degradation (+18%) by solubilization of hydrophobic compounds and increasing activities of oxidoreductases (+27%) and hydrolases (+44%). Biosurfactants perform exceptionally (+45%) by increasing pollutant solubility and altering microbial cell membrane permeability. These findings generalize effective strategies to accelerate microbial degradation of organic pollutants and to optimize remediation conditions in contaminated environments. © 2024 Elsevier Ltd