I do it all the time and it's very cool.
If you're a pro, you can pick a destination location, research live-music venues, and contact them directly about playing a gig while you're in-town.
Another great option is find the open mics near where you're staying.
Plan your trip around the performances and let everything else fall into place.
Another fun thing that enhances these kinds of trips is the keeping of a journal. It's fun to look back over the years at the various venues that I've played. Good times!