Autophagy, a process that captures and degrades intracellular components, can have both tumor suppressive and tumor promoting roles in cancer. Tumor suppression occurs through the elimination of oncogenic protein substrates, toxic unfolded proteins, and damaged organelles. Conversely, autophagy can promote cancer by providing substrates for metabolism and maintaining mitochondrial function. The context-specific role of autophagy in cancer and the underlying mechanisms are crucial for guiding therapeutic interventions. Autophagy disruption leads to the accumulation of ubiquitylated protein aggregates, abnormal organelles, and increased reactive oxygen species, promoting cellular damage and disease. In contrast, autophagy is essential for suppressing p62 accumulation and inappropriate activation of the NRF2 pathway, which can promote survival and tumorigenesis. Autophagy is also crucial for maintaining mitochondrial function and providing substrates for metabolic pathways, particularly in RAS-driven cancers. Stimulation of autophagy may be beneficial for cancer prevention, while inhibition of autophagy can enhance the efficacy of targeted therapies. However, autophagy inhibition may pose cytotoxicity issues and requires further investigation to identify susceptible patient subtypes.Autophagy, a process that captures and degrades intracellular components, can have both tumor suppressive and tumor promoting roles in cancer. Tumor suppression occurs through the elimination of oncogenic protein substrates, toxic unfolded proteins, and damaged organelles. Conversely, autophagy can promote cancer by providing substrates for metabolism and maintaining mitochondrial function. The context-specific role of autophagy in cancer and the underlying mechanisms are crucial for guiding therapeutic interventions. Autophagy disruption leads to the accumulation of ubiquitylated protein aggregates, abnormal organelles, and increased reactive oxygen species, promoting cellular damage and disease. In contrast, autophagy is essential for suppressing p62 accumulation and inappropriate activation of the NRF2 pathway, which can promote survival and tumorigenesis. Autophagy is also crucial for maintaining mitochondrial function and providing substrates for metabolic pathways, particularly in RAS-driven cancers. Stimulation of autophagy may be beneficial for cancer prevention, while inhibition of autophagy can enhance the efficacy of targeted therapies. However, autophagy inhibition may pose cytotoxicity issues and requires further investigation to identify susceptible patient subtypes.