With continuous and aggressive scaling in semiconductor technology, there is an increasing gap between design expectation and manufactured silicon data. Research on DFM (Design for manufacturability), MFD (Manufacturing for Design) and statistical analysis have been investigated in recent years to bridge design and manufacturing. Fundamentally, layout is the final output from the design side and the input to the manufacturing side. It is also the last chance to dramatically modify the design efficiently and economically. In this dissertation, I present the modeling and optimization work on bridging the gap between design expectation and reality, improving performance and enhancing manufacturing yield. I investigate several stages of semiconductor design development including manufacturing process, device, interconnect, and circuit level. In the manufacturing process stage, a novel inverse lithography technology (ILT) is proposed for sub-wavelength lithography resolution enhancement. New intuitive transformations enable the method to gradually converge to the optimal solution. A highly efficient method for gradient calculation is derived based on partially coherent optical models. Dose variation is considered within the ILO process with the min-max optimization method and the computation overhead on dose process variation could be omitted. The methods are implemented in state-of-the-art industrial 32nm lithography environment. After the work in the lithography process stage provides both mask optimization and post-layout silicon image simulation, my work on the first non-rectangular device modeling card extends the post-layout lithography to post-litho electrical calibration. Based on the lithography simulation results, the non-rectangular gate shapes are extracted and their effect is investigated by the proposed non-rectangular device modeling card and post-litho circuit simulation flow. This work is not only the first non-rectangular device modeling card but also compatible with industry standard device models and the parameter extraction flow. Interconnect plays a more critical role in the nanometer scale IC design especially because of its impact on delay. The scattering effect that occurs in nanoscale wires is modeled and different methods of wire sizing/shaping are discussed. Based on closed-form resistivity model for nanometer scale Cu interconnect, new interconnect delay model and wire sizing/shaping strategies are developed. Based on the advanced modeling of process, device and interconnect, circuit level investigation is focused on statistical timing analysis with a new latch delay model. For the first time, both combinational logic and clock distribution circuits are integrated together through statistical timing of latch outputs. This dissertation studies the new phenomena of nanometer scale IC design and manufacture. Starting from the designed layout, through modeling, optimization and simulation, the work moves ahead to the mask pattern and silicon image, calibrates electrical properties of devices as well as circuits. Through above process, we can better connect layout with silicon data to reach design and manufacturing closure. / text