Tumor cell invasion is the key driver of metastatic dissemination, resulting in the development and progression of metastatic tumors at secondary sites, and remains the major cause of cancer-related death. Recent studies suggest that, in addition to protease-mediated degradation and chemotaxis-stimulated migration, tumor invasion is significantly influenced by physical surroundings. How tumor cells decode information about their shape deformation under mechanical stress and adapt their dynamic behavior to escape the confined regions remains largely unknown. This review highlights recent findings that illustrate mechanical cues in confined tumor microenvironment contribute to tumor progression. We also systematically discuss the role of compression-induced deformation in cell membrane topology and cytoskeletal remodeling, as well as its biophysical mechanisms in regulating tumor invasion from a biomechanical perspective.