Recent discoveries in cancer metabolism have revealed promising metabolic targets to modulate cancer progression, drug response, and anti-cancer immunity. Combination therapy, consisting of metabolic inhibitors and chemotherapeutic or immunotherapeutic agents, offers new opportunities for improved cancer therapy. However, it also presents challenges due to the complexity of cancer metabolic pathways and the metabolic interactions between tumor cells and immune cells. Many studies have been published demonstrating potential synergy between novel inhibitors of metabolism and chemo/immunotherapy, yet our understanding of the underlying mechanisms remains limited. Here, we review the current strategies of altering the metabolic pathways of cancer to improve the anti-cancer effects of chemo/immunotherapy. We also note the need to differentiate the effect of metabolic inhibition on cancer cells and immune cells and highlight nanotechnology as an emerging solution. Improving our understanding of the complexity of the metabolic pathways in different cell populations and the anti-cancer effects of chemo/immunotherapy will aid in the discovery of novel strategies that effectively restrict cancer growth and augment the anti-cancer effects of chemo/immunotherapy.