The goal of this proposed research plan is to bring fundamental advances towards micro- and nano-scale mixed-signal design through the development of accurate and efficient simulation framework that enables integrated interconnects, substrate, device, modeling and co-simulation. Full-wave algorithms in the time domain will be the emphasis of this proposed research though the frequency domain techniques will also be investigated. This framework will facilitate the understanding of system level electrical and thermal coupling mechanisms and being used to develop better design practices for IC design engineers. To reduce the complexity of the modeling/simulation task, model-order-reduction (MOR) techniques will be used in a hierarchical fashion to include the traditional semiconductor device effects and characteristics of nano-scale devices. The ultimate objective of this proposed research is to facilitate circuit/system design by developing algorithms and design practices that can be integrated into the IC design flow.