Polluted soils contain a mixture of contaminants. The microorganisms-mediated degradation processes and mechanisms appear to be more complicated than those in a controlled lab environment given that the soil microbiota is diverse and versatile in ecological functioning. In recent years, many researchers have highlighted the adaptation mechanism of the microbiome, biotransformation processes, design of synthetic microbial systems, in situ remediation by microbiomes in mixed organic pollutants contaminated soils, which are important for an understanding of the processes and mechanisms underlying soil remediation. The degradation of mixed organic pollutants is believed to be mainly controlled by the soil microbial community and influenced by their complex ecological networks. Due to the advantages of microbiomes(metabolic synergy and functional complementarity), this paper systematically analyzes the research progress and development trend of microbiome-mediated transformation and remediation mechanisms in organic pollutant co-contaminated soils and presents an outlook on the development of microbiomes in green and sustainable in situ bioremediation of mixed contaminated soils.