Surface pitting is the main quality problem that develops during prolonged storage of sweet cherries. It appears as one or more depressions on the surface of the fruit and is associated with the collapse of cells under the skin of the fruit. However, this physiological disorder is not shown in all cultivars with the same intensity. This research aims to analyze the cell wall disassembly of two cultivars displaying contrasting susceptibility to damage after pitting induction. In addition, we evaluated the metabolomic and transcriptomic changes in sweet cherries during cold storage. Our results show that damage to ‘Sweetheart’ fruit was more severe than damage to ‘Bing’ fruit. No differences were observed in the cell wall composition between nonpitted and pitted cherries; however, the varietal differences during cold storage were the most significant. The resistant cultivar ‘Bing’ showed a longer sidechain of RG-I; instead, ‘Sweetheart’ PME and PG activity was more marked at the beginning of cold storage. The metabolomics analysis revealed several compounds related to the abiotic stress response, such as 3-O-coumaroyl-D-quinic acid, chlorogenic acid, GABA and β-sitosterol. Furthermore, transcriptomics showed a higher expression of stress-related hormones in the susceptible cultivar and cell wall remodeling-related genes in the resistant cultivar. In conclusion, the contrasting susceptivity to surface pitting in sweet cherries can be attributed to the varietal response to cold storage rather than the mechanical stress of pitting induction.