As cancer develops, the surrounding microenvironment undergoes biophysical changes which promote tumor proliferation and invasion, creating a feedback loop of cancer growth and metastasis. The unique biophysical properties of the tumor microenvironment present potential targets in the study, diagnosis, and treatment of cancer. Abbreviation: ECM, extracellular matrix; FA, focal adhesion; LOX, lysyl oxidase; TIMPs, tissue inhibitors of metalloproteinase; MRCS, mechano-responsive cell system; AFM, atomic force microscopy.