Advancements in metabolomic and genomic research tools are revealing new insights into how metabolic networks can influence skeletal muscle fiber composition. In this mini-review, we summarize the recent progress of metabolite-dependent signaling pathways and transcriptional regulators that control glycolytic and oxidative metabolism and ultimately influence the type of fibers in muscle depots. These mechanisms expand the role of metabolites beyond that of basic building blocks of cellular components, and illustrate how particular metabolites can take an active role in regulating metabolic homeostasis and fiber adaptation. As new metabolite-dependent mechanisms emerge, ongoing metabolomic studies have begun to help explain why distinct metabolic pathways are used in different biological contexts and widen the view of seminal observations like the Warburg effect.