Here, we demonstrate that silenced VDAC1 expression in BC using two BC mouse models, subcutaneous UM-UC3 cells and chemically induced BC using N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN), resulted in metabolism reprogramming and led to inhibited tumor growth, as well as modulations of the tumor microenvironment (TME), including reduced angiogenesis, extracellular matrix (ECM), tumor-associated microphages, inhibited stemness, and epithelial mesenchymal transition (EMT). The gene discussed is VDAC1; the disease is neoplasm.