Metastatic melanoma is the most aggressive and deadliest type of skin cancer. Over the past decades, new therapies targeting mutations in these tumors have been developed. Some of the most promising of these therapies target a protein called B-Raf (BRAF) and are called BRAF inhibitors. These inhibitors are effective initially but, over time, patients develop resistance to them, and they are no longer effective. Recognizing this challenge, we propose an innovative approach targeting an important resistance mechanism called metabolic reprogramming. Through this mechanism, cells are able to switch their mode of obtaining energy. In the case of melanoma cells, they usually obtain their energy through a pathway called glycolysis, which allows them to obtain energy quickly. However, when exposed to BRAF inhibitors, these cells have been shown to prefer a pathway called oxidative phosphorylation (OXPHOS), which has been associated with resistance to drugs and metastasis in the setting of cancer. We propose using a drug called atovaquone, which inhibits OXPHOS, against melanoma cells. Atovaquone is an FDA-approved drug with minimal side effects that has been shown to have anti-cancer effects against other types of cancers, such as ovarian and breast cancer, but has not been studied in melanoma. We will first study the effects of atovaquone by itself and then will study the effects of atovaquone in combination with BRAF inhibitors. We hypothesize that atovaquone will have anti-cancer effects against melanoma and that these effects will be stronger in combination with BRAF inhibitors. This innovative approach will study an unexplored treatment avenue and will provide insight into the effects of inhibiting the metabolic pathway of OXPHOS in melanoma.