The circadian clock is entrained by metabolic cues and exerts pervasive temporal control in metabolic processes. The intricate interplay between circadian clock with nutrient signals orchestrates homeostasis. Our research focuses on deciphering the molecular and signaling pathways underlying tissue-intrinsic clocks circuits in driving metabolic tissue functional capacity. Recent studies uncovered the nutrient-sensing role of clock that governs metabolic substrate metabolism. Mechanistic interrogations of clock modulation of nutrient metabolism in adipose tissue and skeletal muscle will be discussed, together with our recent foray into targeting these mechanisms for disease applications.