Despite advances in breast cancer treatment, metastatic disease remains incurable and is of particular concern in patients with triple negative breast cancer. Both aberrant metabolic signaling and physical properties of the microenvironment have been independently defined as hallmarks of cancers, and experimental evidence suggests that they may be functionally linked. However, the current lack of physiologically relevant culture models that capture relevant physical details prevents studying the specific mechanisms that link metabolic reprogramming, the physical microenvironment, and clinical outcomes of malignancy. By leveraging capabilities of five different institutions the Cornell Physical Sciences Oncology Center (PSOC) will interrogate the multiscale biological and physical (structural, mechanical, and solute transport) mechanisms regulating tumor metabolism and function, as well as the consequences on tumor development, metastatic progression, and therapy response. The new physical sciences-driven mechanistic insights that will be generated by our PSOC promise to inform a more integrated approach to the prevention, diagnosis, and treatment of breast cancer.