Over the past decade, researchers have highlighted the importance of mechanical cues of the metastatic niche such as matrix stiffness, topography, mechanical stresses, and deformation on cells in influencing tumor growth and proliferation. Understanding the cellular and molecular basis and fine-tuning the mechano-response of cancer cells to this niche could lead to new and novel therapeutic interventions. In this review, we discuss the importance of mechanical cues surrounding tumor microenvironment that govern the growth and progression of cancer. We also highlight some emergent principles underlying the mechanosensing and mechanotransduction mechanisms that link cellular responses such as gene expression to phenotypic changes arising from such external cues. Recent technological advancements to visualize, quantify, model, and test these crucial steps with great precision will further advance our understanding of this phenomenon. We will conclude by showcasing potential applications of mechanobiology in controlling cancer growth as alternative cancer treatment regimes.