Vibrios represent a natural contaminant of seafood products. , , and are the most hazardous species to human health. Given the worldwide consumption of mollusc products, reliable detection of species is recommended to prevent human vibriosis. In this study, culture-dependent and -independent methods were compared and integrated to implement knowledge of the Manila clam community composition. Here, 16S and AH metabarcoding were applied to compare the microbial communities of homogenate clam samples (culture-independent method) and their culture-derived samples plated on three different media (culture-dependent method). In addition, a subset of plated clam samples was investigated using shotgun metagenomics. Homogenate metabarcoding characterized the most abundant taxa (16S) and species (AH). Culture-dependent metabarcoding detected the cultivable taxa, including rare species. Moreover, marine agar medium was found to be a useful substrate for the recovery of several species, including the main human pathogenic ones. The culture-dependent shotgun metagenomics detected all the main human pathogenic species and a higher number of vibrios with respect to the AH metabarcoding. The study revealed that integration of culture-dependent and culture-independent methods might be a valid approach for the characterization of biodiversity.