The article reviews the therapeutic evolution in HR+/HER2- breast cancer, focusing on targeted therapy and endocrine therapy. It highlights the significance of HR+/HER2- breast cancer as the most common subtype, accounting for 74% of breast cancer cases. The review discusses the epidemiology, classification, and treatment strategies for HR+/HER2- breast cancer, emphasizing the role of targeted therapies such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and antibody-drug conjugates (ADCs), as well as endocrine therapies like aromatase inhibitors, selective estrogen receptor modulators (SERMs), and selective estrogen receptor degraders (SERDs). The mechanisms of action, clinical trials, and potential synergistic effects of these treatments are detailed, along with their side effects and management strategies. The article also covers the use of ovarian suppression in premenopausal women and the ongoing research in PROTACs for targeting estrogen receptor degradation. Overall, the review underscores the ongoing advancements and challenges in treating HR+/HER2- breast cancer.The article reviews the therapeutic evolution in HR+/HER2- breast cancer, focusing on targeted therapy and endocrine therapy. It highlights the significance of HR+/HER2- breast cancer as the most common subtype, accounting for 74% of breast cancer cases. The review discusses the epidemiology, classification, and treatment strategies for HR+/HER2- breast cancer, emphasizing the role of targeted therapies such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and antibody-drug conjugates (ADCs), as well as endocrine therapies like aromatase inhibitors, selective estrogen receptor modulators (SERMs), and selective estrogen receptor degraders (SERDs). The mechanisms of action, clinical trials, and potential synergistic effects of these treatments are detailed, along with their side effects and management strategies. The article also covers the use of ovarian suppression in premenopausal women and the ongoing research in PROTACs for targeting estrogen receptor degradation. Overall, the review underscores the ongoing advancements and challenges in treating HR+/HER2- breast cancer.