Lung metastases are detected in more than half of patients with metastatic tumors, yet it remains largely unknown why the lung environment is particularly permissive to metastases. Here, we describe that pulmonary aspartate promotes lung metastasis by rewiring the translatome of disseminating cancer cells. We found that both patients and mice with breast cancer have high concentrations of aspartate in their lung interstitial fluid. This extracellular aspartate activates the ionotropic N-methyl-D-aspartate (NMDA) receptor in cancer cells, which induces CREB-dependent mRNA expression of deoxyhypusine hydroxylase (DOHH). The latter is essential for hypusination, a posttranslational modification required for the activity of the non-classical translation initiation factor eIF5A. In turn, a translational program with TGF- signaling as a central hub promotes collagen remodeling in the disseminated breast cancer cells. We detect key aspects of this mechanism in lung metastases from patients with breast cancer. In summary, we discover that pulmonary aspartate increases with breast cancer and induces a signaling cascade that promote lung metastatic outgrowth.