It’s about 4 hours drive from Venice to Pienza, most of it on a 4-6 lane freeway.
I don’t know about you but I often drive from the San Francisco Bay Area to LA (about 6 hours drive) without spending the night midway in Los Banos or Coalinga, which by the way smells like sh.t due to the intense cattle raising along I-5.
It’s up to you, but I think you can drive it in one shot, maybe stopping along the way for a pit stop at a freeway rest area, which in Italy can be very fancy, with Autogrill chain restaurants and shopping, in addition to restroom and fuel stations, as you can see here or here