Coral reefs face severe threats from climate change, making it crucial to understand the mechanisms behind coral resilience. Metabolomics is a powerful tool for studying cellular mechanisms and adaptation, but current approaches have been hampered by low sensitivity, dependence on single analytical platforms, and limited annotation of the full complement of metabolites produced by the coral host and bacterial and algal (Symbiodiniaceae) symbionts. We present a high-throughput, low-biomass metabolomics platform that was used to investigate the mechanisms of the coral heat stress response. Using a combination of gas-, HILIC-, and anion-exchange chromatographies coupled with quadrupole or high-resolution mass spectrometry, we reveal > 300 unique metabolites, providing comprehensive coverage on the coral and Symbiodiniaceae central carbon metabolism. This platform assessed the heat stress responses of Galaxea fascicularis and Pocillopora acuta (32 °C compared to control 25 °C) over one week. Photosynthetic health, cell density, and protein measurements were taken to assess the level of stress the corals experienced. We integrated stable isotope labeling (e.g., 13C, 15N) to trace fluxes of metabolites between the host and symbionts to elucidate the molecular basis of coral heat stress response. These analyses highlighted major changes in the coral host/symbiont metabolome in response to heat stress.