As fabrication technology keeps advancing, many deep submicron (DSM) effects have become increasingly evident and can no longer be ignored in Very Large Scale Integration (VLSI) design. In this dissertation, we study several deep submicron problems (eg. coupling capacitance, antenna effect and delay variation) and propose optimization techniques to mitigate these DSM effects in the place-and-route stage of VLSI physical design. The place-and-route stage of physical design can be further divided into several steps: (1) Placement, (2) Global routing, (3) Layer assignment, (4) Track assignment, and (5) Detailed routing. Among them, layer/track assignment assigns major trunks of wire segments to specific layers/tracks in order to guide the underlying detailed router. In this dissertation, we have proposed techniques to handle coupling capacitance at the layer/track assignment stage, antenna effect at the layer assignment, and delay variation at the ECO (Engineering Change Order) placement stage, respectively. More specifically, at layer assignment, we have proposed an improved probabilistic model to quickly estimate the amount of coupling capacitance for timing optimization. Antenna effects are also handled at layer assignment through a linear-time tree partitioning algorithm. At the track assignment stage, timing is further optimized using a graph based technique. In addition, we have proposed a novel gate splitting methodology to reduce delay variation in the ECO placement considering spatial correlations. Experimental results on benchmark circuits showed the effectiveness of our approaches.