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Bioenergetic metabolism is a key regulator of cellular function and signaling activity but the exact roles of nutrient utilization and energy production in embryonic development remain unknown. Here we investigated the metabolic pathways and deciphered the role of carbon metabolism required for the development of neural crest cells (NCC), a migratory stem cell population of the vertebrate embryo. We uncovered that glucose oxidation constitutes the prominent metabolic signature of trunk NCC and supports their delamination, migration, and proliferation. Additionally, we found that glycolysis, mitochondrial respiration and the pentose phosphate pathway are all mobilized downstream of glucose uptake. These metabolic pathways do not support specific cellular processes but cooperate and are integrated to accomplish epithelium-to-mesenchyme transition, adhesion, locomotion and proliferation. Moreover, using different nutrient supplies (glucose vs. pyruvate) we show that glucose is crucial to modulate NCC migration and adaptation to environmental stiffness, control NCC stemness and drive their fate decisions through regulation of specific gene expression. Our data establish that NCC development is instructed by metabolic cues that mobilize defined metabolic pathways cooperating together in response to nutrient availability.SUMMARY STATEMENTHere we show that neural crest cell migration and fate decisions rely primarily on glucose oxidation for energy production and mobilize multiple cooperating metabolic pathways for their biosynthetic needs and execution of gene programs.