M2-polarized tumor-associated macrophages (M2 TAMs) promote gastric cancer progression by secreting exosomes containing the long non-coding RNA MALAT1. These exosomes induce aerobic glycolysis in gastric cancer cells, enhancing their proliferation, metastasis, and chemoresistance. MALAT1 is enriched in M2 TAM exosomes and is transferred to gastric cancer cells, where it stabilizes the δ-catenin protein by inhibiting its ubiquitination and degradation via β-TRCP. Additionally, MALAT1 acts as a miR-217-5p sponge to upregulate HIF-1α expression, activating the β-catenin and HIF-1α signaling pathways, which further promote glycolysis. Dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages via exosome-mediated delivery of siRNA significantly suppresses gastric cancer growth and improves chemosensitivity in mouse models. These findings suggest that M2 TAM-derived exosomes promote gastric cancer progression through MALAT1-mediated regulation of glycolysis, offering a potential therapeutic target for gastric cancer.M2-polarized tumor-associated macrophages (M2 TAMs) promote gastric cancer progression by secreting exosomes containing the long non-coding RNA MALAT1. These exosomes induce aerobic glycolysis in gastric cancer cells, enhancing their proliferation, metastasis, and chemoresistance. MALAT1 is enriched in M2 TAM exosomes and is transferred to gastric cancer cells, where it stabilizes the δ-catenin protein by inhibiting its ubiquitination and degradation via β-TRCP. Additionally, MALAT1 acts as a miR-217-5p sponge to upregulate HIF-1α expression, activating the β-catenin and HIF-1α signaling pathways, which further promote glycolysis. Dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages via exosome-mediated delivery of siRNA significantly suppresses gastric cancer growth and improves chemosensitivity in mouse models. These findings suggest that M2 TAM-derived exosomes promote gastric cancer progression through MALAT1-mediated regulation of glycolysis, offering a potential therapeutic target for gastric cancer.