Stiffness of the extracellular matrix (ECM) is known to direct cell behaviors such as adhesion, migration, proliferation, and differentiation. Due to this knowledge, it is crucial to obtain specific biologically relevant mechanical properties of engineered ECM that has been synthesized for biomedical applications. In this chapter, we would like to discuss three common synthesized ECMs: hydrogels, electrospun nanofibers, and self-assembling nanofibers, by reviewing the fabrication approaches for tuning their mechanical properties. For hydrogels, mechanical properties can be tuned through changes in the hydrogel crosslinking process, fabrication method, or pre-gelled composition. Mechanical properties of electrospun nanofibers can be modulated through the alteration of viscosity, electrical charge, solvent selection, environmental conditions, or fiber alignment. Mechanical properties of self-assembling nanofibers can be controlled through changes in divalent ion concentration, amino acid sequence, or solution pH. However, some of the approaches used to alter matrix stiffness often result in unwanted changes in other properties of the material. For example, changes in crosslinking density result in hydrogels with altered diffusivity that can cause inadequate oxygen and nutrient transfer to cells. Similarly, increasing the fiber diameter of electrospun nanofibers enhances mechanical properties but may not be favorable for regulation of phenotypic cell behavior. Therefore, several engineering approaches have been developed to tune mechanical properties of synthetic ECM without or with minimally affecting other material properties. By studying mechanical properties of synthetic ECM, engineered structures with tunable mechanics can be fabricated for applications of regenerative medicine as well as for studies of development biology.