Symbiosis essentially forms the cornerstone of complex life on earth. Spearheading symbiosis research in the last few decades include the exploration of diverse mutualistic animal-bacterial associations from marine habitats. Yet, many facets of symbiotic associations remain under-examined. Here we investigated marine bivalves of the genera Bathymodiolus and Codakia, inhabiting hydrothermal vents and shallow water ecosystems, respectively, and their bacterial symbionts. The symbionts reside intracellularly within gill epithelia and supply their host with chemoautotrophically fixed carbon. They oxidize reduced substrates like sulfide (thiotrophic symbionts) and methane (methanotrophic symbionts) from surrounding fluids for energy generation. The nature of interactions between host and symbiont at the metabolic and physical level, as well as between the holobiont and its environment remain poorly understood. In vitro cultivations of both symbiont and host are difficult till date, hampering the feasibility of targeted molecular investigations. We bypassed culture-based experiments by proteogenomically investigating physically separated fractions of host and symbiont cell components for the bivalves Bathymodiolus azoricus, Bathymodiolus thermophilus and Codakia orbicularis. Using these enrichments, we sequenced the symbionts’ genomes and established semi-quantitative host-symbiont (meta-) proteomic profiles. This combined approach enabled us to resolve symbiosis-relevant metabolic ...