The advent of 21st century medicine will be based on a comprehensive approach to achieving the highly sensitive and specific detection of diseases, as well as the development of novel materials and devices based on biotic-abiotic interfacing as interventional modalities. Novel technologies that enable early identification of physiological changes will serve as a gateway tool for the proper treatment of these disorders. Toward the realization of these technologies, microfabrication and nanofabrication methods have been applied to biomedical systems that allow scientists to interact with cellular and molecular systems on their native size scales. Future enabling systems will build on the foundation composed of such devices. With respect to the envisioned fruition of biofunctional nanomaterials and systems, foundational studies of biological systems and molecules, as well as their interfacing with biocompatible materials, have produced a domain of components that can be integrated and engineered toward eventual cytomimetic materials for transplantation. In addition, the potential underscoring of their future applications in nanoscale medicine is based on the ability to engineer and design intelligent membrane/protein self-assembling and organization phenomena that are typically found in nature into these artificial composite systems. These devices will provide a powerful suite of solutions with broad applicabilities in nanomedicine, for example, (1) the use of concomitant protein functionality toward energy production and the powering of medical implants and (2) replacement of damaged cells (e.g., heart and neuron) with implantable biologically intelligent engineered materials. This work will examine key advances in the areas of diagnostics and synthetic biology that have led to visionary contributions to next-generation medicine. Furthermore, we present 2 devices that will contribute to the realization of compelling biosensing and biofunctional material technologies. These systems include advanced diagnostic platforms for whole-cell detection, as well as copolymeric materials that have been functionalized by the coupled activity of their embedded membrane proteins. They are envisioned to successfully bridge the gap between foundational scientific progress and the realization of rapid point-of-care disease assessment and biofunctional devices with higher-order behavior.