The article provides a comprehensive review of HER2-targeted therapies, focusing on their mechanisms of action, representative drugs, clinical trials, recent advancements, and future research directions. HER2, a member of the epidermal growth factor receptor (EGFR) family, is associated with the development of various cancers, including breast, gastric, non-small cell lung (NSCLC), bladder, and colorectal cancers. The overexpression or amplification of the HER2 gene leads to abnormal signaling pathways, promoting tumor growth and proliferation. HER2-targeted therapies include monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs). Monoclonal antibodies, such as trastuzumab and pertuzumab, prevent HER2-containing heterodimer formation and modulate downstream signaling. TKIs inhibit the kinase activity of HER2, blocking downstream signaling pathways. ADCs combine an antibody with a cytotoxic agent, enhancing the therapeutic effect by delivering the drug directly to cancer cells. The article highlights the significant advancements in HER2-targeted therapies, particularly the approval of ADCs like T-DM1 and T-DXd for breast cancer. These ADCs have shown remarkable efficacy in various clinical trials, extending progression-free survival and overall survival in patients with HER2-positive cancers. Additionally, the article discusses the challenges of primary and acquired resistance to HER2-targeted therapy and strategies to overcome these challenges, including the development of novel drugs and drug combinations. The review also emphasizes the importance of accurate HER2 status determination and the need for standardized criteria across different tumors. Liquid biopsy techniques, such as ctDNA, are being explored to assess HER2 status non-invasively, addressing the limitations of traditional biopsy methods. In conclusion, HER2-targeted therapies have become a crucial component of cancer treatment, with ongoing research aimed at improving their efficacy and expanding their indications.The article provides a comprehensive review of HER2-targeted therapies, focusing on their mechanisms of action, representative drugs, clinical trials, recent advancements, and future research directions. HER2, a member of the epidermal growth factor receptor (EGFR) family, is associated with the development of various cancers, including breast, gastric, non-small cell lung (NSCLC), bladder, and colorectal cancers. The overexpression or amplification of the HER2 gene leads to abnormal signaling pathways, promoting tumor growth and proliferation. HER2-targeted therapies include monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs). Monoclonal antibodies, such as trastuzumab and pertuzumab, prevent HER2-containing heterodimer formation and modulate downstream signaling. TKIs inhibit the kinase activity of HER2, blocking downstream signaling pathways. ADCs combine an antibody with a cytotoxic agent, enhancing the therapeutic effect by delivering the drug directly to cancer cells. The article highlights the significant advancements in HER2-targeted therapies, particularly the approval of ADCs like T-DM1 and T-DXd for breast cancer. These ADCs have shown remarkable efficacy in various clinical trials, extending progression-free survival and overall survival in patients with HER2-positive cancers. Additionally, the article discusses the challenges of primary and acquired resistance to HER2-targeted therapy and strategies to overcome these challenges, including the development of novel drugs and drug combinations. The review also emphasizes the importance of accurate HER2 status determination and the need for standardized criteria across different tumors. Liquid biopsy techniques, such as ctDNA, are being explored to assess HER2 status non-invasively, addressing the limitations of traditional biopsy methods. In conclusion, HER2-targeted therapies have become a crucial component of cancer treatment, with ongoing research aimed at improving their efficacy and expanding their indications.