The taxonomic and functional composition of the eastern oyster microbiome was profiled by amplicon sequencing targeting the V4 region of the 16S rRNA gene and shotgun metagenomics. Six tissue types (gut, mantle, gill, hemolymph, pallial fluid, and inner shell swab) were profiled using amplicon sequencing. Gut tissue of individual oysters as well as pooled gut samples that underwent microbial enrichment were analyzed using shotgun metagenomics. Metagenome-assembled genomes were obtained representing members of the Mollicutes and Chlamydiae. This project provides an in-depth understanding of the oyster microbiome through tissue-specific community profiling and genome-wide functional annotations.