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Vibrios represent a natural contaminant of seafood products. <i>V. alginolyticus</i>, <i>V. cholerae</i>, <i>V. parahaemolyticus</i> and <i>V. vulnificus</i> are the most hazardous species to human health. Given the worldwide consumption of mollusc products, reliable detection of <i>Vibrio</i> 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 <i>Vibrio</i> community composition. Here, 16S and <i>rec</i>A<i>-pyr</i>H 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 <i>Vibrio</i> species (<i>rec</i>A<i>-pyr</i>H). 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 <i>Vibrio</i> species, including the main human pathogenic ones. The culture-dependent shotgun metagenomics detected all the main human pathogenic <i>Vibrio</i> species and a higher number of vibrios with respect to the <i>rec</i>A<i>-pyr</i>H metabarcoding. The study revealed that integration of culture-dependent and culture-independent methods might be a valid approach for the characterization of <i>Vibrio</i> biodiversity.