In general, HIF activity increases glycolysis and related carbohydrate pathways (e.g. pentose phosphate pathway and glycogen metabolism) as well as lactate export while suppressing mitochondrial O₂-dependent metabolism. Amino acid, acetate, and fatty acid uptake are increased to fuel processes that are essential for formation of ROS scavengers and Krebs cycle intermediates. This metabolic rewiring not only allows rapid proliferation and protects cells from ROS-induced damage but also contributes to formation of breast cancer stem cells and generation of an acidic and nutrient-depleted immunosuppressive microenvironment. Drugs with their respective targets or nonpharmaceutical, patient-centered strategies that target the rewired metabolism in breast cancer are listed in blue text. The key notes their furthest stage of (pre)clinical development in the breast cancer setting and/or evaluation in clinical trial(s) as monotherapy or as combination therapy. 1CM, one-carbon metabolism; 2-DG, 2-deoxyglucose; ACC, acetyl-CoA carboxylase; ACSS, acetyl-CoA synthetase; ALDO, aldolase; BNIP3, BCL2- and adenovirus E1B 19-kDa–interacting protein 3; CA, carbonic anhydrase; ETC, electron transport chain; FABP, fatty acid–binding protein; FAO, fatty acid oxidation; FASN, fatty acid synthase; G6PD, glucose-6-phosphate dehydrogenase; GAA, α-1,4-glucosidase; GBE, glycogen branching enzyme; GLUT, glucose transporter; GSH, glutathione; GYS, glycogen synthase; HK, hexokinase; α-KG, α-ketoglutarate; LDHA, lactate dehydrogenase A; MCT, monocarboxylate transporter; NBC, Na⁺-bicarbonate cotransporter; NHE, Na⁺/H⁺ exchanger; PDK, pyruvate dehydrogenase kinase; PFK, phosphofructokinase; PGK, phosphoglycerate kinase; PHGDH, phosphoglycerate dehydrogenase; PPP, pentose phosphate pathway; PYG, glycogen phosphorylase; SLC, solute carrier; SNAT, sodium-coupled neutral amino acid transporter.