Vascular smooth muscle cells (SMC) play an essential role in remodeling the vasculature during disease progression. Induced pluripotent stem cells (iPSC) provide an attractive approach to obtain autologous SMC source for patient-specific disease modeling. Here we discuss the current methods to 1) derive functional SMC from iPSC, 2) model vascular diseases using SMC generated from patient-derived iPSC, and 3) modulate microenvironmental cues to enhance cellular differentiation and functionality and better mimic the physiological environment. We emphasize that continuous exploration of biomaterial technologies to engineer a more SMC-specific microenvironment will provide further insight on complex vascular diseases.