Thermophiles are referred to as microorganisms with optimal growth temperatures of >60 °C. Over the past few years, a number of studies have been conducted regarding thermophiles, especially using the omics strategies. This review provides a systematic view of the survival physiology of thermophiles from an "omics" perspective, which suggests that the adaptive ability of thermophiles is based on a cooperative mode with multi-dimensional regulations integrating genomics, transcriptomics, and proteomics.