Coral bleaching events from thermal stress are increasing globally in duration, frequency, and intensity. Bleaching occurs when a coral’s algal symbionts are expelled, resulting in a loss of color. While bleaching can result in mortality, some corals survive, reacquire their symbionts, and recover. In this study, we experimentally bleached Montipora capitata to examine molecular and physiological signatures of intrinsic differences between corals that recover (resilient) compared to those that die (susceptible). All corals were collected from the same bay and monitored for eight months post-bleaching to identify genets exhibiting long-term resilience and survival. Using an integrated systems-biology approach that included quantitative mass spectrometry-based proteomics, 16S rRNA of the microbiome, total lipids, symbiont community composition and density, we explored molecular-level mechanisms of tolerance in experimental corals pre- and post-bleaching and identified predictive biomarkers of resilience that distinguish resilient and susceptible corals before thermal-induced bleaching events. Prior to thermal stress, resilient corals were characterized by a more diverse microbiome and increased abundances of proteins essential for carbon and nitrogen acquisition strategies, symbiont retention and acquisition, and pathogen resistance. Susceptible corals had early signs of symbiont rejection and had resorted to using urea uptake pathways for carbon and nitrogen. Further, proteins identified prior to bleaching were amplified after bleaching, suggesting these pathways may be deterministic of a coral’s fate when thermally bleached. Our results have important implications for the future of reefs, revealing molecular factors necessary for surviving thermally-induced bleaching events and identifying promising diagnostic biomarker candidates for coral reef management and restoration applications.