Autophagy, a cellular self-degradation process, plays a critical role in cancer development, drug resistance, and treatment. This review explores the potential of autophagy inhibition as a therapeutic strategy for cancer. Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches. Autophagy inhibitors include Class III PI3K inhibitors, lysosomotropic agents, and autophagosome–lysosome fusion inhibitors. These inhibitors have shown promise in preclinical studies and are being evaluated in clinical trials. CQ and HCQ are the only FDA-approved autophagy inhibitors used in cancer therapy. Clinical trials have shown that CQ and HCQ can enhance the efficacy of chemotherapy in various cancers. However, their clinical efficacy is still under investigation. The review highlights the potential of autophagy inhibitors in cancer therapy and the need for further research to optimize their use.Autophagy, a cellular self-degradation process, plays a critical role in cancer development, drug resistance, and treatment. This review explores the potential of autophagy inhibition as a therapeutic strategy for cancer. Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches. Autophagy inhibitors include Class III PI3K inhibitors, lysosomotropic agents, and autophagosome–lysosome fusion inhibitors. These inhibitors have shown promise in preclinical studies and are being evaluated in clinical trials. CQ and HCQ are the only FDA-approved autophagy inhibitors used in cancer therapy. Clinical trials have shown that CQ and HCQ can enhance the efficacy of chemotherapy in various cancers. However, their clinical efficacy is still under investigation. The review highlights the potential of autophagy inhibitors in cancer therapy and the need for further research to optimize their use.