This study investigates the effect of autochthonous oyster-derived bacteria on mitigating the off-flavors in oyster hydrolysate (OPH) using flavoromics, microbiomics, and non-targeted metabolomics technologies. Results showed that the taste and odor sensory scores of oyster-derived lactic acid bacteria (LAB) fermentation were significantly better than those of commercial fermentation (p < 0.05), scoring 4.14 ± 0.47 and 4.23 ± 0.26, respectively (out of 5). Significant alterations were observed in volatile flavor compounds (VOCs) such as 5-nonanone, 2-undecanone, 3-octanol, 3,6-nonadien-1-ol, phenylethanol, and γ-decalactone. Non-volatile flavor metabolites were mainly represented by a rise in unsaturated fatty acids and a decrease in saturated fatty acids and bitter amino acids (Tyr and Arg). A total of 569 differential metabolites were identified, mainly involved in linoleic acid metabolism, glycerophospholipids, phenylalanine (Phe), tyrosine (Tyr), arginine (Arg), and proline (Pro). Lecithin, Tyr, Phe, histidine (His), Arg, and glutamine (Gln) were identified as flavor precursor compounds for oyster-derived LAB fermentation. High-throughput sequencing clarified the dominant role of oyster-derived LAB in influencing metabolites and precursors during fermentation. This study offers new insights into the mechanisms of flavor development in autochthonous bacteria-inoculated fermented shellfish.