Hepatocellular carcinoma is the most common form of liver cancer, originating from liver cells known as hepatocytes. Many cases of Hepatocelullar carcinoma involve the amplification and over expression of the oncogene c-Myc. c-Myc is a transcription factor that plays a key role in many aspects of cancer including cellular growth and metabolism. Metabolic reprogramming has recently emerged as a fundamental hallmark of cancer. In line with this notion, recent studies have shown that c-Myc can regulate expression of genes associated with the de novo nucleotide biosynthesis and lipogenesis. Based on these studies, we hypothesize that the oncogene c-Myc reprograms nucleotide and lipid metabolism to fuel liver cancer. In this project, we took advantage of an inducible zebrafish model of liver cancer, in which c‑Myc is overexpressed specifically in hepatocytes upon exposure to doxycycline. Using this model, we demonstrated that c-Myc induces hepatomegaly in larvae and liver cancer in adults. In order to examine the impact of c-Myc on metabolism, we applied a metabolomics profiling strategy (Gas Chromatography-Mass Spectrometry/ GC‑MS) on dissected liver tissue, and we found that c-Myc overexpression reprogrammed metabolism. Based on these findings, we used the Tet-On myc zebrafish as a drug discovery platform to screen potential metabolic interventions for efficacy in suppressing c‑Myc-driven hepatomegaly. Strikingly, we identified Mycophenolic acid, Simvastatin, Ezetimibe, and Orlistat as the compounds with the most profound effects in suppressing hepatomegaly driven by c-Myc. Together, our studies highlight the interplay between c‑Myc and metabolism in the context of oncogenic liver growth that could potentially be targeted therapeutically in the future. Furthermore, this work highlights the potential of using zebrafish models of liver cancer to identify therapeutic strategies that target the metabolic vulnerabilities of liver tumours.