Recent engineering technologies have transformed traditional perspectives of cancer to include the important role of the extracellular matrix (ECM) in recapitulating the malignant behaviors of cancer cells. Novel biomaterials and imaging technologies have advanced our understanding of the role of ECM density, structure, mechanics, and remodeling in tumor cell-ECM interactions in cancer biology and have provided new approaches in the development of cancer therapeutics. Here, we review emerging technologies in cancer ECM biology and recent advances in engineered systems for evaluating cancer therapeutics and provide new perspectives on how engineering tools present an opportunity for advancing the modeling and treatment of cancer. This review offers the cell biology and cancer cell biology communities insight into how engineering tools can improve our understanding of cancer ECM biology and therapeutic development.