Desert plants have evolved remarkable adaptations to survive in arid environments, where water scarcity and extreme temperatures pose significant challenges to life. The desert moss Syntrichia caninervis stands out as an exemplary model of extreme desiccation tolerance (DT), offering invaluable insights into plant adaptation to water deficit. This study presents a comprehensive multi-omics analysis of S. caninervis during controlled dehydration and rehydration process, integrating transcriptomic, proteomic, and metabolomic data to elucidate the molecular mechanisms underlying its remarkable resilience. Our findings reveal a sophisticated, multilayered response characterized by extensive transcriptional reprogramming (3,153 differentially expressed genes), dynamic proteome remodeling (873 differentially expressed proteins), and strategic metabolic reconfiguration (185 differentially abundant metabolites). Key adaptations include the coordinated downregulation of photosynthetic processes, upregulation of stress-responsive genes and proteins, accumulation of protective metabolites, and enhancement of antioxidant systems. Notably, we observed significant temporal asynchrony between transcript and protein levels, underscoring the complexity of post-transcriptional regulation in stress responses. The core mechanisms of S. caninervis DT comprises cellular protection and metabolic dormancy during dehydration, followed by efficient repair and recovery processes upon rehydration. These findings not only advance our understanding of plant evolution and adaptation to extreme environments but also identify potential targets for enhancing drought tolerance in crops and exploring plant survival under extreme environment. By deciphering the molecular basis of extreme DT, this research opens new avenues for addressing agricultural challenges in water-limited environments and expands our knowledge of plant life's adaptability to harsh terrestrial.