Frailty is a common geriatric syndrome and a risk factor for many diseases, even mortality. However, the specific molecular biomarkers for diagnosis and therapeutic targets of frailty are still lacking. Studies focusing on molecular profiling in the development of frailty will help address this problem and others. Recently, a series of high-throughput “-omics” technologies have been used to measure thousands of dynamic molecules, including genetic, metabolic, microorganic variables and so on. These omics data extend our understanding of the pathological processes that change with frailty. In this review, we introduce frailty syndrome and summarize current advancements in the applications of omics technologies in the field of frailty.