Biophysical properties associated with the microenvironment of a tumor has been recognized as an important modulator for cell behaviour and function. Particularly, tissue rigidity is important during tumor carcinogenesis as it affects the tumor’s ability to metastasis. Multiple downstream pathways are affected with a difference in rigidity of the extracellular matrix. The insight into tumor mechanosignalling represents a promising field that may lead to novel approaches for cancer diagnostics. Measurement of rigidity of the extracellular matrix or the tissue is a potential diagnostics approach for cancer detection. Altered extracellular matrix states persist for a long period of time and have lower heterogeneity compared to protein or genetic markers, therefore are more reliable as biomarkers. On the other hand, measurement of different kinase associated proteins or transcripts provide an early insight into potential transition of cells towards metastasis. Co-localization of transcriptional factors like YAP/TAZ provide an insight to determine if the cells are undergoing metastatic changes. This review explains the unique biophysical properties of the tumor microenvironment that present the potential targets for the diagnosis of cancer.