Abstract: Recent years have witnessed significant advancements in the perioperative trea-tment of locally advanced gastric cancer (LAGC), yet numerous challenges persist. Current research focuses primarily on the precise application of immunotherapy, breakthroughs in targeted therapy, optimization of multidisciplinary comprehensive treatment models, and the selection of postopera-tive adjuvant therapy regimens. Although immunotherapy has achieved remarkable progress in the treatment of advanced gastric cancer, its application in the perioperative setting remains controver-sial, particularly regarding its long-term survival benefits. In terms of targeted therapy, the applica-tion of drugs targeting human epidermal growth factor receptor-2 and Claudin 18.2 in the periopera-tive setting for LAGC still requires further validation. Additionally, the optimization of multidisci-plinary comprehensive treatment models, such as the long-term survival benefits of neoadjuvant chemoradiotherapy combined with perioperative chemotherapy, remains unclear. There are also many disputes surrounding the selection of postoperative adjuvant therapy regimens and surgical strategies following neoadjuvant treatment, including the extent of lymph node dissection. Addres-sing these issues will help further optimize the perioperative treatment strategies for LAGC, thereby improving patient survival rates and quality of life. Therefore, the authors explore in depth the key issues and relevant strategies for perioperative treatment of LAGC.