Agelas oroides (Schmidt, 1864) is a widely distributed Mediterranean sponge inhabiting shallow coralligenous formationsas well as mesophotic depths. Although this species has been extensively studied for its specialized metabolites (e.g. bromo-pyrrole alkaloids), little is known about its internal organization, cellular components and associated prokaryotes. This study aims at describing the histology and cytology of Agelas oroides, while providing in depth (DNA metabarcoding) analysis of the high abundant microbial community associated with this species. Macroscopically differentiable sponge body parts (orange external and off-white internal) were analyzed separately. Additionally, sponge eukaryotic and prokaryotic cells were organized in two enriched fractions following a separation by centrifugation. Electron microscopy observations revealed low quantities of sponge cells in the ectosome compared to the choanosome. A. oroides has low sponge cell diversity and these cells are loosely distributed in the mesohyl. Two types of amoeboid cells harbor big vacuoles and specific spherical inclusions. The prokaryotic community is primarily composed of bacteria (35 phyla) with Pseudomonadota, Acidiobacteria, and Candidatus Poribacteriota being the most abundant. This community exhibits a homogeneous composition across the different body parts. The archaea community is represented by 8 Amplicon Sequence Variants (ASVs), all of them assigned to the Nitrosopumilus genus (Thermoproteota phylum). Statistical differences in microbial composition and abundance were noted between the enriched eukaryotic and prokaryotic fractions. Each fraction was characterized by specific core communities suggesting differential functionalities of the assigned ASVs. This work sets the basis for future analyses aiming to correlate sponge eukaryotic cells and prokaryotic diversities with the chemical composition of this sponge species.