Due to the rapid development of IC technology the traditional packaging concepts are making a transition into more complex system integration techniques in order to enable the constantly increasing demand for more functionality, performance, miniaturisation and lower cost. These new packaging concepts (as e.g. system in package, 3D integration, MEMS-devices) will have to combine smaller structures and layers made of new materials with even higher reliability. As these structures will more and more display nano-features, a coupled experimental and simulative approach has to account for this development to assure design for reliability in the future. A necessary ''nano-reliability'' approach as a scientific discipline has to encompass research on the properties and failure behaviour of materials and material interfaces under explicit consideration of their micro-and nano-structure and the effects hereby induced. It uses micro-and nano-analytical methods in simulation and experiment to consistently describe failure mechanisms over these length scales for more accurate and physically motivated lifetime prediction models. This paper deals with the thermo-mechanical reliability of microelectronic components and systems and methods to analyse and predict it. Various methods are presented to enable lifetime prediction on system, component and material level, the latter promoting the field of nano-reliability for future packaging challenges in advanced electronics system integration.