Cancer in children have a high burden and affects the children’s lives as well as their families for almost the rest of their lives. Moreover, pediatric cancer patients are prone to developing other malignancies in adulthood. Even though the incidence rates vary in different areas, creating a proper therapeutic approach for these patients has been challenging for several decades, and different strategies have been introduced with promising results. It is well established that cancer cells have altered metabolic needs, and some pathways are augmented in these cells. Cancer cells’ dysregulated metabolism and therapeutic vulnerabilities can be promising targets for killing malignant cells. Among the metabolic pathways, glycolysis, lipogenesis, amino acids metabolism, and nucleotide biosynthesis are essential targets. Different treatment approaches and agents are provided to help the first-line therapeutic choices in curing or controlling the cancer. In this chapter, the metabolism of different types of cancers is discussed, and therapeutic agents targeting the metabolic pathways are provided based on the current evidence and findings.