Corals reefs support hyperdiverse ecosystems and build natural offshore structures that protect our coastlines from storm surge and coastal inundation. The corals that build these structures are able to do so by forming intimate symbioses with dinoflagellates in the family Symbiodiniaceae that provide photosynthetically fixed carbon to the coral host as an energy source. However, when ocean temperatures increase (particularly during marine heatwaves that are becoming more intense due to climate change), this symbiosis breaks down, the algae are expelled, and corals lose their coloration, a phenomenon popularly known as bleaching. As a result of bleaching, corals can quickly suffer mass mortality, destabilizing the entire reef ecosystem and threatening its survival. After decades of research on bleaching, our understanding of the genomic basis for bleaching, for both corals, their algal symbionts, and other partners (i.e., the coral holobiont) remains very limited. What is missing is a granular understanding of the genomics of bleaching linked to the functional changes that occur during the process. To fill this knowledge gap, we need to comprehensively characterize the transcriptomic response of the coral holobiont at the single-cell level in order to capture the functional genomic response of the different members of the coral holobiont during bleaching events. Not doing so limits our understanding of the bleaching process and consequently our ability to develop strategies to improve the survival trajectories of coral reefs in the current climate crisis. Our goal is to develop an approach that can be used to scrutinize the transcriptomic response of the coral holobiont at the single-cell level. Our central hypothesis is that not all coral and symbiont cell types have the same transcriptomic profile. Therefore, they will not have the same response to bleaching. We formulated this hypothesis based on the available single-cell transcriptomic data from basal animals related to corals that show different transcriptomic profiles indifferent cell lines and based on the few transcriptomic studies on coral symbiotic algae and bacteria. Our rationale is that having an integrated granular understanding of the coral holobiont’s transcriptomic response across coral cell types and symbionts during a bleaching event will transform our understanding of coral bleaching and potentially help us identify better strategies for intervention (NASEM 2019).