AbstractMeat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat nutrition and flavor are poorly understood. Here, 3431 metabolites and 702 volatiles in 423 skeletal muscle samples are profiled from a gradient consanguinity segregating population generated by Pekin duck × Liancheng duck crosses using metabolomic approaches. The authors identified 2862 metabolome‐based genome‐wide association studies (mGWAS) signals and 48 candidate genes potentially modulating metabolite and volatile levels, 79.2% of which are regulated bycis‐regulatory elements. The level of plasmalogen is significantly associated withTMEM189encoding plasmanylethanolamine desaturase 1. The levels of 2‐pyrrolidone and glycerophospholipids are regulated by the gene expression ofAOX1andACBD5, which further affects the levels of volatiles, 2‐pyrrolidone and decanal, respectively. Genetic variations inGADL1andCARNMT2determine the levels of 49 metabolites including L‐carnosine and anserine. This study provides novel insights into the genetic and biochemical basis of skeletal muscle metabolism and constitutes a valuable resource for the precise improvement of meat nutrition and flavor.