This Special Issue on “Selected Papers from IEEE ICASI 2018” includes excellent papers presented at the IEEE ICASI 2018 regarding the “applied system innovation” topic. Mechanical engineering and design innovations are both academic and practical engineering fields, which involve systematic technological materialization through scientific principles and engineering designs. Technological innovations in mechanical engineering include IT-based intelligent mechanical systems, mechanics and design innovations, and applied materials in nanosciences and nanotechnology. The aim is to encourage the attendees at the IEEE ICASI 2018 to publish their experimental and theoretical research relating to applied system innovation.