The surface nanoarchitecture provides spatially and temporally resolved stimuli response of the material, and offers defined control over the behavior of biomolecules and cells at the solid-liquid interface. Here, the focus is on metal-based systems that are interesting for biomedical applications. Intelligence of the surface is suggested to be achieved through its nanostructuring for stimuli responsive properties. Spatial and temporal cell performance at the surface, provided by the surface nanoarchitecture, offers advanced bio-applications of metal-based materials, such as implantation, lab-on-chip and organ-on-chip, biosensors, smart biomaterials and drug delivery systems. Spatial control is achieved by surface patterning. Temporal control is accessed through the application of stimuli responsive switchable surface chemistry, sensitive to external parameters: temperature, pH, light, electric and magnetic field, ionic strength, surrounding medium (hydrogels in water), multi-trigger response, and response to products of the cell metabolism. The key issue is the prospect in the formation of self-regulating “intelligent” surface cell interactions: biomimetic of natural systems.