I live in Lower Pacific Heights and commute to South San Francisco. It is difficult and time-consuming to go to SSF on public transportation, but easy by car. The commute back home can be slow depending on Bay Bridge traffic, which backs up all SF-incoming traffic on 101.
If you are a bicyclist, you can ride down to BART on Mission Street or Glen Park to take it outbound to SSF. This will take you twice the time of driving -- and if your office is near the Bay, the winds are very difficult in the evening.