Challenge can be many I would specify few.
1. Placement : As frequency increase then PD engineer gets shorter time period per cycle b/w FF which will result in tight constraints... Need a placement strategy by PD engineer.
2.. CTS... If your placement is not good then you have high skew and latency.
3. Routing : Routing congestion .. GRC map
4. Timing: Even if your placement cells are near and they are violating by 50ps. engineer starts adding buffer or upsize the cells... which can result in increase in the utilization locally.