Proteomics and metabolomics can be used to efficiently and conveniently assess proteins and metabolites during microbial degradation of pollutants; these analytical techniques are closely correlated and mutually confirmed and provide a means to explore degradation pathways. The degradation pathways and regulatory characteristics of Microbacterium sp. M.CSW3 for the metabolism of benzopyrene (BaP) alone and in the presence of phenanthrene and pyrene were investigated using these omics. Proteomics results showed that CLP protease, ABC transporter, aldehyde dehydrogenase, and enoyl-CoA hydratase were important for the metabolism of polycyclic aromatic hydrocarbons (PAHs). Five pathways for the microbial degradation of benzopyrene were suggested by metabolomics, and phenanthrene was identified as an intermediate metabolite. Further, correlation analysis showed that the two stress environments inhibited the biosynthesis of bacterial amino acids. The glycolysis/gluconeogenesis and fatty acid degradation pathways played a positive role in energy acquisition and PAHs degradation. Addition of low-molecular-weight PAHs promoted the production of related enzyme systems and also make the degradation of BaP more thorough. This study provides efficient concepts and methods for the exploration of degradation mechanisms of high-molecular-weight PAHs and co-metabolism of mixed PAHs.