Breast cancer cells secrete miR-199b-5p, which hijacks the neuron-astrocyte metabolic coupling to promote brain metastasis. This miRNA is highly expressed in the blood of breast cancer patients with brain metastases and is found in extracellular vesicles (EVs) from brain-tropic breast cancer cells. miR-199b targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons), disrupting the metabolic coupling between neurons and astrocytes. This disruption leads to the extracellular retention of glutamate, glutamine, and lactate, which promotes cancer cell growth. The study shows that miR-199b is associated with brain metastasis in breast cancer patients and is secreted more by brain-tropic cancer cells. EVs containing miR-199b are taken up by brain cells, leading to the downregulation of EAAT2, SNAT2, and MCT2, which are critical for metabolite transport. This results in increased extracellular levels of glutamate, glutamine, and lactate, supporting cancer cell growth. In vivo experiments confirm that miR-199b enhances brain metastasis by altering brain metabolism. The study highlights the role of miR-199b in reprogramming neural metabolism to facilitate brain metastasis and suggests potential therapeutic strategies targeting this mechanism.Breast cancer cells secrete miR-199b-5p, which hijacks the neuron-astrocyte metabolic coupling to promote brain metastasis. This miRNA is highly expressed in the blood of breast cancer patients with brain metastases and is found in extracellular vesicles (EVs) from brain-tropic breast cancer cells. miR-199b targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons), disrupting the metabolic coupling between neurons and astrocytes. This disruption leads to the extracellular retention of glutamate, glutamine, and lactate, which promotes cancer cell growth. The study shows that miR-199b is associated with brain metastasis in breast cancer patients and is secreted more by brain-tropic cancer cells. EVs containing miR-199b are taken up by brain cells, leading to the downregulation of EAAT2, SNAT2, and MCT2, which are critical for metabolite transport. This results in increased extracellular levels of glutamate, glutamine, and lactate, supporting cancer cell growth. In vivo experiments confirm that miR-199b enhances brain metastasis by altering brain metabolism. The study highlights the role of miR-199b in reprogramming neural metabolism to facilitate brain metastasis and suggests potential therapeutic strategies targeting this mechanism.