Cells express hundreds of different types of receptors, which they use to continuously monitor their chemical and mechanical microenvironments. Stem cells and cancer cells are particularly sensitive to microenvironmental cues because their interactions have profound effects on stem cell potency and tumorigenesis, respectively. Unlike conventional tissue culture in wells and dishes, microtechnology with dimensions on the cellular scale can be combined with materials, chemicals, physiological flows, and other effectors to provide high levels of control in a format more flexible than macroscale in vitro or in vivo systems, revealing stimulation-specific responses of stem cells and cancer cells. Microtechnology-integrated biology enable the simultaneous control of multiple numbers of biological microenvironmental factors in a high-throughput manner. In this review we present representative examples of the use of microtechnology systems to regulate the mechanical, chemical, topological, adhesive, and other environments of individual stem cells and cancer cells. We then explore the possibilities for simultaneous multimodal control of combinations of these environmental factors.