Blood vessels are crucial for tissue development, functionality, and homeostasis and are typically a determinant in the progression of healing and regeneration. The tissue microenvironment provides physicochemical cues that affect cellular function, and the study of the microenvironment can be accelerated by the engineering of approaches capable of mimicking various aspects of the microenvironment. In this review, we introduce the major components of the vascular niche and focus on the roles of oxygen and the extracellular matrix (ECM). We demonstrate how vascular engineering approaches enhance our understanding of the microenvironment's impact on the vasculature towards vascular regeneration and describe the current limitations and future directions towards clinical utilization.