Recent advances in nanotechnology, material chemistry, molecular biology, and bioimaging have provided unprecedented opportunities for diagnosis and treatment of human diseases. Cells have central roles in tissue regeneration and pathological progression. The rational engineering of cells for sensible implementation of diagnosis and therapy is critical for the management of complex diseases. In this talk, I will present our progress of using concise biological approaches to engineer cells as living biosensors to non-invasively evaluate chemotherapy efficacy in cancer research, and as therapeutic modalities for vasculargenesis and neurogenesis in regeneration medicine. I will also share our recent development of biomimetic 3D scaffolds in engineering stem cell differentiation in vitro. Our goal is to develop effective chemical and biological strategies in conjunction of advanced nano/microfabrication technologies to engineer cells and use them for drug discovery and development.