Studies on the impact of ocean acidification on marine organisms involve exposing organisms to future acidification scenarios which has limited relevance for coastal calcifiers living in a mosaic of habitats. Identification of tipping points beyond which detrimental effects are observed is a widely generalizable proxy of acidification susceptibility at the populational level. This approach is limited to a handful of studies that focus on only a few macro-physiological traits, thus overlooking the whole organism response. Here we develop a framework to analyze the broad macro-physiological and molecular responses over a wide pH range in juvenile oyster. We identify low tipping points for physiological traits at pH 7.3-6.9 that coincide with a major reshuffling in membrane lipids and transcriptome. In contrast, a drop in pH affects shell parameters above tipping points, likely impacting animal fitness. These findings were made possible by the development of an innovative methodology to synthesize and identify the main patterns of variations in large -omic datasets, fitting them to pH and identifying molecular tipping-points. We propose the broad application of our framework to the assessment of effects of global change on other organisms.