In this paper, surface activated nanointegration of computational, electrical, optical, and mechanical structures for intelligent telemetry, communication, and sensing systems is described. The design approach and integration of top-down systems and bottom-up devices is considered with the need for biologically compatible bonding. For the simplified interface between bottom-up and top-down design a bus-bar unit architecture is presented. Emerging biomedical applications using intelligent sensors for remote patient monitoring and systems for rehabilitation comparing surface vs. implanted sensors are considered. Requirements for nanointegration of biomedical systems are suggested. Diverse combinations of rigid and flexible substrates of copper, gold, gallium arsenide, gallium phosphide and liquid crystal polymer were bonded by using two different nanobonding techniques. In these techniques, the surface cleaning with/without simultaneous deposition of nano-adhesion layers and contact in ultra-high vacuum/high vacuum were accomplished. These nanobonding technologies provide void-free, strong, and nanometer scale covalent bonding at room temperature or at low temperatures (∼240 °C), and do not require chemicals, adhesives, or high external pressure. A considerable electrical current conduction and low loss of the nanobonded laminate was observed at high frequency. This investigation reveals that a biocompatible, high performance, and miniaturized systems may be realized for intelligent, implantable biomedical sensors because of the strong bond, low toxicity and favorable electrical properties in surface activated nanobonding.