Human epidermal growth factor receptor 2 (HER2) gastric cancer (GC) is a distinct subtype of GC, accounting for 10‑20% of all cases of GC. Although the development of the anti‑HER2 monoclonal antibody trastuzumab has markedly improved response rates and prognosis of patients with HER2 advanced GC (AGC), drug resistance remains a considerable challenge. Therefore, dynamic monitoring of HER2 expression levels can facilitate the identification of patients who may benefit from targeted therapy. Besides trastuzumab, DS‑8201 and RC48 have been applied in the treatment of HER2 AGC, and several novel anti‑HER2 therapies are undergoing preclinical/clinical trials. At present, combination immunotherapy with anti‑HER2 agents is used as the first‑line treatment of this disease subtype. New promising approaches such as chimeric antigen receptor T‑cell immunotherapy and cancer vaccines are also being investigated for their potential to improve clinical outcomes. The current review provides new insights that will guide the future application of anti‑HER2 therapy by summarizing research progress on targeted therapy drugs for HER2 AGC and combination treatments.