Lactate dehydrogenase A (LDHA) regulates tumor-macrophage symbiosis to promote glioblastoma progression. Glioblastoma is a highly aggressive brain tumor with poor prognosis, and current therapies have failed to significantly improve survival. This study shows that LDHA-mediated glycolysis in glioblastoma cells promotes macrophage infiltration into the tumor microenvironment (TME), which in turn supports tumor growth and survival. Macrophages, in turn, produce LDHA-containing extracellular vesicles that enhance glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis significantly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of patient samples confirms that LDHA and its downstream signals are potential biomarkers correlating with macrophage density. The study reveals that LDHA activates the ERK-YAP1/STAT3 pathway, upregulating CCL2 and CCL7, which recruit macrophages to the TME. Macrophage-derived LDHA-containing extracellular vesicles further promote tumor growth by maintaining the ERK-YAP1/STAT3-CCL2/CCL7 axis. In vivo experiments show that LDHA inhibition extends survival in glioblastoma mouse models. Clinical data support the correlation between LDHA, YAP1, STAT3, CCL2, and CCL7 with macrophage abundance and survival in glioblastoma patients. These findings highlight the therapeutic potential of targeting LDHA-mediated tumor-macrophage symbiosis in glioblastoma.Lactate dehydrogenase A (LDHA) regulates tumor-macrophage symbiosis to promote glioblastoma progression. Glioblastoma is a highly aggressive brain tumor with poor prognosis, and current therapies have failed to significantly improve survival. This study shows that LDHA-mediated glycolysis in glioblastoma cells promotes macrophage infiltration into the tumor microenvironment (TME), which in turn supports tumor growth and survival. Macrophages, in turn, produce LDHA-containing extracellular vesicles that enhance glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis significantly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of patient samples confirms that LDHA and its downstream signals are potential biomarkers correlating with macrophage density. The study reveals that LDHA activates the ERK-YAP1/STAT3 pathway, upregulating CCL2 and CCL7, which recruit macrophages to the TME. Macrophage-derived LDHA-containing extracellular vesicles further promote tumor growth by maintaining the ERK-YAP1/STAT3-CCL2/CCL7 axis. In vivo experiments show that LDHA inhibition extends survival in glioblastoma mouse models. Clinical data support the correlation between LDHA, YAP1, STAT3, CCL2, and CCL7 with macrophage abundance and survival in glioblastoma patients. These findings highlight the therapeutic potential of targeting LDHA-mediated tumor-macrophage symbiosis in glioblastoma.