In the last five decades, the number of transistors on a chip has increased exponentially in accordance with the Moore's law, and the semiconductor industry has followed this law as long-term planning and targeting for research and development. However, as the transistor feature size is further shrunk to sub-14nm nanometer regime, modern integrated circuit (IC) designs are challenged by exacerbated manufacturability and reliability issues. To overcome these grand challenges, full-chip modeling and physical design tools are imperative to achieve high manufacturability and reliability. In this paper, we will discuss some key process technology and VLSI design co-optimization issues in nanometer VLSI.