Abstract: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has achieved significant survival benefits in clinical studies of advanced gastric cancer. This combination has rewritten the treatment strategy for patients with gastric cancer. However, some patients with gastric cancer are insensitive or develop immune tolerance to immunotherapy or develop treatment-related adverse reactions. Thus, it is essential to choose a superior population of ICIs, which, when combined with chemotherapy, may aid in managing patients with advanced gastric cancer. Based on research on the progress of first-line treatment of advanced gastric cancer, we respectively reviewed the efficacy-related biomarkers of PD-1/PD-L1 inhibitors, combined with chemotherapy, for patients with HER-2 positive advanced gastric cancer and HER-2 negative advanced gastric cancer. Other potential biomarkers, and their current application status, problems, challenges, and development trends, were discussed. In the future, developing a combined evaluation model of multiple biomarkers and establishing a prediction model may accurately identify the immunotherapy advantage population.