The past decade has witnessed a rapid accumulation of evidence showing that hypoxic microenvironment, which is typical during cancer development, plays key roles in regulating cancer cell metabolism. In this review, we will focus on the role of hypoxic response, particularly, its master regulator hypoxia-inducible factor-1, in regulating glucose, lipid, as well as amino acid metabolism in cancer cells. We will also discuss the therapeutic opportunities by targeting specific pathways that facilitate metabolic reprogramming in cancer cells.