Gastric cancer (GC) remains a significant contributor to cancer-related mortality, with a notable gender disparity and rising incidence among younger individuals. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, play crucial roles in the development and progression of GC. *Helicobacter pylori* (Hp) infection and Epstein–Barr virus (EBV) infection are key environmental factors that influence these epigenetic changes. DNA methylation, particularly in CpG islands, is a common mechanism for tumor-suppressor gene silencing or oncogene activation. Histone modifications, such as methylation and acetylation, also contribute to gene expression regulation and cell growth. Non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), serve as epigenetic regulators and are involved in various cellular processes. The interplay between these epigenetic mechanisms and environmental factors provides insights into the complex biology of GC. Ongoing clinical trials are evaluating the efficacy of next-generation epigenetic drugs, and various approaches, including miRNA inhibitors and targeted nanoparticles, are being developed to enhance treatment efficacy and overcome resistance. The identification of specific biomarkers, such as serum RNA molecules and gastric fluids, holds promise for non-invasive diagnostic, prognostic, and therapeutic applications.Gastric cancer (GC) remains a significant contributor to cancer-related mortality, with a notable gender disparity and rising incidence among younger individuals. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, play crucial roles in the development and progression of GC. *Helicobacter pylori* (Hp) infection and Epstein–Barr virus (EBV) infection are key environmental factors that influence these epigenetic changes. DNA methylation, particularly in CpG islands, is a common mechanism for tumor-suppressor gene silencing or oncogene activation. Histone modifications, such as methylation and acetylation, also contribute to gene expression regulation and cell growth. Non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), serve as epigenetic regulators and are involved in various cellular processes. The interplay between these epigenetic mechanisms and environmental factors provides insights into the complex biology of GC. Ongoing clinical trials are evaluating the efficacy of next-generation epigenetic drugs, and various approaches, including miRNA inhibitors and targeted nanoparticles, are being developed to enhance treatment efficacy and overcome resistance. The identification of specific biomarkers, such as serum RNA molecules and gastric fluids, holds promise for non-invasive diagnostic, prognostic, and therapeutic applications.