Skeletal muscle is a major site of whole-body fat and carbohydrate catabolism due to its mass and its metabolic activity. Among the key biological mechanisms associated with muscle energy metabolism are not only mechanical force and hence physical performances, but also mitochondrial activity and the regulation of muscle insulin sensitivity, for instance. Therefore, muscle energy metabolism plays an important role in human subjects for the apparition of metabolic disorders. It is also important for the production of healthy meat from muscles of farm animals due to its impact on meat quality traits through the regulation of animal physiology. This paper aims to argue that genomics has huge potential to better understand muscle energy metabolism despite some technical limitations. Genome-wide studies of differential expression may help indeed to define gene or protein markers of muscle metabolic properties and hence of metabolic diseases and animal phenotypic traits. However, the vast amount of information derived from expression studies using the new genomics tools remains to be analyzed and combined with physiological data. Indeed, integrated muscle physiology using modeling tools from genes to in vivo metabolite levels and fluxes should help to understand the metabolic regulation of fuels at the muscle and whole body levels.