Gastric cancer (GC) remains one of the most common deadly malignancies worldwide. Recently, several targeted therapeutics for treating unresectable or metastatic GC have been developed. Comprehensive characterization of the molecular profile and of the tumor immune microenvironment of GC has allowed researchers to explore promising biomarkers for GC treatment and has enabled a new paradigm in precision-targeted immunotherapy. In this article, we review established and promising new biomarkers relevant in GC, with a focus on their clinical implications, diagnostic methods, and the efficacy of targeted agents.