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Gastric cancer (GC) is one of the most widespread causes of cancer-related death worldwide. Recently, emerging implied that gastric cancer stem cells (GCSCs) play an important role in the initiation and progression of GC. This subpopulation comprises cells with several features, such as self-renewal capability, high proliferating rate, and ability to modify their metabolic program, which allow them to resist current anticancer therapies. Metabolic pathway intermediates play a pivotal role in regulating cell differentiation both in tumorigenesis and during normal development. Thus, the dysregulation of both anabolic and catabolic pathways constitutes a significant opportunity to target GCSCs in order to eradicate the tumor progression. In this review, we discuss the current knowledge about metabolic phenotype that supports GCSC proliferation and we overview the compounds that selectively target metabolic intermediates of CSCs that can be used as a strategy in cancer therapy.