The advancement of fundamental sciences in recent decades has led to an increased focus on the prediction of phenomena occurring at the micro and nano scales. Micro- and nanostructures have a wide range of applications in various fields, such as aerospace and automobiles, and are widely used in nano- and micro-sized systems and devices, such as biosensors, nanoactuators, and nanoprobes. The design of these structures relies on a complete understanding of their physical and mechanical behaviors. Mechanics plays a crucial role at the micro- and nanoscales, from the generation of nanostructures to the properties of nanocomposite materials and the manufacturing and design of machines, structures, sensors, actuators, fluidics, and more. This Special Issue aims to bring together high-quality papers that advance the field of micro- and nanostructures and systems through the use of modern computational and analytical methods, in conjunction with experimental techniques, for their analysis, design, manufacture, maintenance, quality, and reliability.