Smart micro/nano systems will foster a revolution in health and environmental management, with the final objective of improving security and quality of life. At the same time, they will create a large market of components and systems, and a renewed perspective for electronic design and manufacturing companies. Such systems will be the fundamental building blocks of wearable and ambient systems, to gather and integrate heterogeneous data in real time and to operate and communicate in a wireless and ultra low power mode. The design of these systems will be enabled by the hybridization of manufacturing technologies which enables us to attain unprecedented levels performance as well as to integrate electronic and fluidic circuits with sensors and actuators. To accomplish this ambitious goal, new technologies and architectures must be matched and tailored to the operational environment by solving novel an challenging design and optimization problems, through the creation of novel design methodologies and tools.