Elucidating the role of prokaryotic symbionts in mediating host physiology has emerged as an important area of research. Since oysters are the world’s most heavily cultivated bivalve molluscs, numerous studies have applied molecular techniques to understand the taxonomic and functional diversity of their associated bacteria. Here, we expand on this research by assessing the composition and putative functional profiles of prokaryotic communities from different organs/compartments of the black-lipped pearl oyster Pinctada margaritifera, a commercially important shellfish valued for cultured pearl production in the Pacific region. Seven tissues, in addition to mucous secretions, were targeted from P. margaritifera individuals: the gill, gonad, byssus gland, haemolymph, mantle, adductor muscle, mucus, and gut. Richness of bacterial Operational Taxonomic Units (OTUs) and phylogenetic diversity differed between host tissues, with mucous layers displaying the highest richness and diversity. This multi-tissues approach permitted the identification of consistent microbial members, together constituting the core microbiome of P. margaritifera, including Alpha- and Gammaproteobacteria, Flavobacteriia, and Spirochaetes. We also found a high representation of Endozoicimonaceae symbionts, indicating that they may be of particular importance to oyster health, survival and homeostasis, as in many other coral reef animals. Our study demonstrates that the microbial communities and their associated predicted functional profiles are tissue specific. Inferred physiological functions were supported by current physiological data available for the associated bacterial taxa specific to each tissue. This work provides the first baseline of microbial community composition in P. margaritifera, providing a solid foundation for future research into this commercially important species and emphasises the important effects of tissue differentiation in structuring the oyster microbiome.