Seawater temperature rise in French Polynesia has repeatedly resulted in the bleaching of corals and giant clams. Because giant clams possess distinctive ectosymbiotic features, they represent a unique and powerful model for comparing molecular pathways involved in 1) maintenance of symbiosis and 2) acquisition of thermo‐tolerance among coral reef organisms. Herein, we explored the physiological and transcriptomic responses of the clam hosts and their photosynthetically active symbionts over a 65‐day experiment in which clams were exposed to either normal or environmentally relevant elevated seawater temperatures. Additionally, we used metabarcoding data coupled with in situ sampling/survey data to explore the relative importance of holobiont adaptation (i.e., a symbiont community shift) versus acclimation (i.e., physiological changes at the molecular level) in the clams’ responses to environmental change. We finally compared transcriptomic data to publicly available genomic datasets for Symbiodiniaceae dinoflagellates (both cultured and in hospite with the coral Pocillopora damicornis) to better tease apart the responses of both hosts and specific symbiont genotypes in this mutualistic association. Gene module preservation analysis revealed that the function of the symbionts’ photosystem II was impaired at high temperature, and this response was also found across all holobionts and Symbiodiniaceae lineages examined. Similarly, epigenetic modulation appeared to be a key response mechanism for symbionts in hospite with giant clams exposed to high temperatures, and such modulation was able to distinguish thermo‐tolerant from thermo‐sensitive Cladocopium goreaui ecotypes; epigenetic processes may, then, represent a promising research avenue for those interested in coral reef conservation in this era of changing global climate.