Autophagy, a cellular recycling process, plays a dual role in cancer therapy by either promoting cell survival or inducing cell death. It is increasingly recognized as a key mechanism in response to metabolic and therapeutic stresses, influencing cancer cell survival and drug resistance. Autophagy can be prodeath or prosurvival, depending on the context, and its regulation is crucial for enhancing chemotherapy efficacy. The PI3K/mTOR and AMPK pathways are central to autophagy regulation, with mTOR inhibiting and AMPK promoting autophagy. Autophagy is induced by various stresses, including ER stress, hypoxia, and nutrient deprivation, and can contribute to chemotherapy resistance or enhance drug efficacy. Autophagy inhibitors like chloroquine (CQ) and hydroxychloroquine (HCQ) are being explored for their ability to overcome resistance by modulating autophagy. Clinical trials show that CQ and HCQ, when combined with chemotherapy, can improve outcomes in cancers such as breast, colorectal, and glioblastoma. However, the exact role of autophagy in cancer remains complex, with ongoing research into its mechanisms and potential as a therapeutic target. Understanding autophagy's dual role is essential for developing effective strategies to enhance chemotherapy and improve patient outcomes.Autophagy, a cellular recycling process, plays a dual role in cancer therapy by either promoting cell survival or inducing cell death. It is increasingly recognized as a key mechanism in response to metabolic and therapeutic stresses, influencing cancer cell survival and drug resistance. Autophagy can be prodeath or prosurvival, depending on the context, and its regulation is crucial for enhancing chemotherapy efficacy. The PI3K/mTOR and AMPK pathways are central to autophagy regulation, with mTOR inhibiting and AMPK promoting autophagy. Autophagy is induced by various stresses, including ER stress, hypoxia, and nutrient deprivation, and can contribute to chemotherapy resistance or enhance drug efficacy. Autophagy inhibitors like chloroquine (CQ) and hydroxychloroquine (HCQ) are being explored for their ability to overcome resistance by modulating autophagy. Clinical trials show that CQ and HCQ, when combined with chemotherapy, can improve outcomes in cancers such as breast, colorectal, and glioblastoma. However, the exact role of autophagy in cancer remains complex, with ongoing research into its mechanisms and potential as a therapeutic target. Understanding autophagy's dual role is essential for developing effective strategies to enhance chemotherapy and improve patient outcomes.