Sarcopenia is a systemic disease with progressive and generalized skeletal muscle dysfunction defined by age-related low muscle mass, high content of muscle slow fibers, and low muscle function. Muscle phenotypes and sarcopenia risk are heritable; however, the genetic architecture and molecular mechanisms underlying sarcopenia remain largely unclear. In recent years, significant progress has been made in determining susceptibility loci using genome-wide association studies. In addition, recent advances in omics techniques, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, offer new opportunities to identify novel targets to help us understand the pathophysiology of sarcopenia. However, each individual technology cannot capture the entire view of the biological complexity of this disorder, while integrative multi-omics analyses may be able to reveal new insights. Here, we review the latest findings of multi-omics studies for sarcopenia and provide an in-depth summary of our current understanding of sarcopenia pathogenesis. Leveraging multi-omics data could give us a holistic understanding of sarcopenia etiology that may lead to new clinical applications. This review offers guidance and recommendations for fundamental research, innovative perspectives, and preventative and therapeutic interventions for sarcopenia.