This study investigates the role of exosomes derived from M2 tumor-associated macrophages (M2 TAMs) in promoting gastric cancer progression. The research finds that M2 TAMs-derived exosomes induce aerobic glycolysis in gastric cancer cells, enhancing their proliferation, metastasis, and chemoresistance. MALAT1, a long non-coding RNA, is enriched in these exosomes and is transferred to gastric cancer cells via exosomes. MALAT1 stabilizes the δ-catenin protein and upregulates HIF-1α expression, both of which contribute to glycolysis. Mechanistically, MALAT1 interacts with δ-catenin to suppress its ubiquitination and degradation, and it also acts as a sponge for miR-217-5p to upregulate HIF-1α. The activation of β-catenin and HIF-1α signaling pathways by MALAT1 leads to enhanced aerobic glycolysis in gastric cancer cells. In vivo studies show that targeting MALAT1 in both gastric cancer cells and macrophages using siRNA-packaged exosomes significantly suppresses gastric cancer growth and improves chemosensitivity. These findings suggest that M2 TAMs-derived exosomal MALAT1 promotes gastric cancer progression through glycolysis regulation, providing a potential therapeutic target for gastric cancer.This study investigates the role of exosomes derived from M2 tumor-associated macrophages (M2 TAMs) in promoting gastric cancer progression. The research finds that M2 TAMs-derived exosomes induce aerobic glycolysis in gastric cancer cells, enhancing their proliferation, metastasis, and chemoresistance. MALAT1, a long non-coding RNA, is enriched in these exosomes and is transferred to gastric cancer cells via exosomes. MALAT1 stabilizes the δ-catenin protein and upregulates HIF-1α expression, both of which contribute to glycolysis. Mechanistically, MALAT1 interacts with δ-catenin to suppress its ubiquitination and degradation, and it also acts as a sponge for miR-217-5p to upregulate HIF-1α. The activation of β-catenin and HIF-1α signaling pathways by MALAT1 leads to enhanced aerobic glycolysis in gastric cancer cells. In vivo studies show that targeting MALAT1 in both gastric cancer cells and macrophages using siRNA-packaged exosomes significantly suppresses gastric cancer growth and improves chemosensitivity. These findings suggest that M2 TAMs-derived exosomal MALAT1 promotes gastric cancer progression through glycolysis regulation, providing a potential therapeutic target for gastric cancer.