A study published in *Nature Cell Biology* reveals that breast cancer cells secrete microRNA-122 (miR-122) into extracellular vesicles, which reprogram glucose metabolism in the premetastatic niche to promote cancer metastasis. miR-122 suppresses glucose uptake in niche cells by downregulating the glycolytic enzyme pyruvate kinase (PKM), thereby reducing glucose availability for cancer cells. This mechanism allows cancer cells to prioritize glucose utilization for their own growth while limiting the energy resources of surrounding cells. In vivo experiments show that miR-122 secreted by cancer cells enhances metastasis by altering glucose metabolism in distant organs such as the brain and lungs. Inhibition of miR-122 in vivo restores glucose uptake in these organs and reduces metastatic incidence. The study highlights the role of miR-122 in reprogramming systemic energy metabolism to support cancer progression. The findings suggest that miR-122 could serve as a predictive biomarker and therapeutic target for metastatic breast cancer. The research underscores the importance of understanding how cancer cells manipulate the metabolic environment of the premetastatic niche to facilitate metastasis.A study published in *Nature Cell Biology* reveals that breast cancer cells secrete microRNA-122 (miR-122) into extracellular vesicles, which reprogram glucose metabolism in the premetastatic niche to promote cancer metastasis. miR-122 suppresses glucose uptake in niche cells by downregulating the glycolytic enzyme pyruvate kinase (PKM), thereby reducing glucose availability for cancer cells. This mechanism allows cancer cells to prioritize glucose utilization for their own growth while limiting the energy resources of surrounding cells. In vivo experiments show that miR-122 secreted by cancer cells enhances metastasis by altering glucose metabolism in distant organs such as the brain and lungs. Inhibition of miR-122 in vivo restores glucose uptake in these organs and reduces metastatic incidence. The study highlights the role of miR-122 in reprogramming systemic energy metabolism to support cancer progression. The findings suggest that miR-122 could serve as a predictive biomarker and therapeutic target for metastatic breast cancer. The research underscores the importance of understanding how cancer cells manipulate the metabolic environment of the premetastatic niche to facilitate metastasis.