Cancer is a group of diseases characterized by the uncontrolled growth of cells and is caused by the accumulation of genetic mutations that contribute to cell division, cell growth, and the DNA repair system. According to the American Cancer Society, more than 1.9 million new cancer cases will be diagnosed in 2022, hence there is a need to study new molecular mechanisms leading to tumorigenesis and develop novel treatment options.While significant research has been done to understand the underlying mechanisms, cancer still poses challenges as it 1) resists cell death, 2) activates metastasis, 3) sustains proliferative signaling, and 4) deregulates cellular metabolism. The present work explores the cancer-supporting role of apoptosis-inducing factor (AIF), a mitochondrial flavoprotein positioned at the convergence of the four hallmarks of cancer. AIF was initially characterized as an effector of caspase-independent death; however, increasing evidence has identified the physiological role of AIF in a variety of cancer, including colorectal, prostate, and pancreatic cancer. Expanding AIF activity studies in additional cancers, such as breast cancer, revealed the capability of AIF to modulate the consumption of biochemical substrates other than glucose, thus deregulating cellular metabolism. These alterations suggest the role of AIF in controlling a switch from metabolic flexibility to metabolic dependency, which can be exploited for therapeutic interventions. Moreover, AIF might be involved in mitochondrial biogenesis of breast cancer, unreported in cancer tested so far. In addition to their metabolic function, AIF serves as a signaling molecule that promotes cadherin switching in a 3-dimensional cell culture model of pancreatic ductal adenocarcinoma, which is associated with tumor growth. Finally. When grown in 3-dimensional culture conditions, pancreatic cancer cells were sensitized to a metabolic inhibitor in an AIF-dependent manner. Altogether, these AIF activities are functionally dissociable and demonstrate that AIF-mediated therapy has promise as a next-generations cancer treatment strategy.