Progress in our knowledge of tumor mechanisms and complexity led to the understanding of the physical parameters of cancer cells and their microenvironment, including the mechanical, thermal, and electrical properties, solid stress, and liquid pressure, as critical regulators of tumor progression and potential prognostic traits associated with clinical outcomes. The biological hallmarks of cancer and physical abnormalities of tumors are mutually reinforced, promoting a vicious cycle of tumor progression. A comprehensive analysis of the biological and physical tumor parameters is critical for developing more robust prognostic and diagnostic markers and improving treatment efficiency. Like the biological tumor traits, physical tumor features are characterized by inter-and intratumoral heterogeneity. The dynamic changes of physical tumor traits during tumor progression and as a result of tumor treatment highlight the necessity of their spatial and temporal analysis in clinical settings. This review focuses on the biological basis of the tumor-specific physical traits, the state-of-the-art methods of their analyses, and the perspective of clinical translation. The importance of tumor physical parameters for disease progression and therapy resistance, as well as current treatment strategies to monitor and target tumor physical traits in clinics, is highlighted.