Pitaya (Selenicereus spp.), recognized for its economic significance and nutritional properties, undergoes rapid quality decline after harvest. This study elucidates the mechanisms driving quality reduction in pitaya during low-temperature storage, utilizing a multi-level approach spanning phenotypic, physiological, metabolic, and transcriptomic assessments. Throughout storage, the pericarp's cell wall degraded, resulting in pericarp thinning, reduced fruit firmness, water loss, and starch content decline. Simultaneously, there is also a reduction in soluble solids, monosaccharides, and malic acid content. Additionally, color changes occur in the fruit flesh. Antioxidant enzyme activity patterns point towards a stress reaction within the fruit. Metabolomic and transcriptomic data implicate genes associated with cell wall integrity and glycolysis in quality diminishment, concurrent with fluctuations in corresponding metabolites. Additionally, we propose that the imbalance of various metabolites, especially monosaccharides, organic acids, lipids, and benzenoids, contributes to the deterioration of pitaya's taste during storage. Thus, emphasizing strategies such as strengthening the cell wall, regulating metabolic rates, and minimizing water loss is crucial to enhance pitaya storage performance.