Tuscany to Rome?

Tuscany where? It's a large region. And along which route?
There are lots of choices but it depends on where you are coming from and which route you take.

You are driving into Rome? Really? You'd better memorize the ZTL sign!

Anyway if "Tuscany" means South of Florence you could stop in Siena, Orvieto, Viterbo or the Lake of Bracciano. Do not leave anything in the trunk, visible or not doesn't matter.

I take it you have a redeye flight from North America landing in Florence early in the morning? If so, you'll be jetlagged so you are wise to take a break.

Arezzo is the first place I'd think of as a pleasant town where you can stop for lunch, stretch your legs, and generally get acclimated to Italy. Others who've been there in recent years can probably give you more specific advice about parking and where to find a restaurant that suits you. If you want your stopping place to be nearer to Rome, consider Montepulciano or Orvieto.

Be aware that it may take longer than you expect to collect your luggage, get your rental car, and get going the correct direction on the highway. Similarly, driving into Rome will likely involve traffic jams.

But -- is there a reason why you want/need a car for this leg of your trip? If you're going to be staying in Rome for several days (as your mention of an apartment rental implies), a car will be a nuisance. Why not take the train?

Where in Tuscany?

I'm sorry, I should have been more specific; we'll be staying in Venice & driving to Castellini in Chianti for our Tuscan stay. The last time we stayed in Rome after our road trip, we dropped the car off in the suburbs & took a taxi to our Apt. We also brought a driving wheel lock and we've never left anything in our car unless we can view it from the restaurant. Orvieto sounds 1/2 way and have never been so that's a good suggestion.
Thank you,
Jean

It might help people to know where in Tuscany to where in Rome since those are both big places. But to start you out, I liked Pitigliano and the nearby areas- look up Citta del Tufo. The towns are small enough to see a couple or do some hiking on the Etruscan trails after lunch, but they might be a little far off the beaten path (the highways) depending on the route you'd want to take.

(Edited to note that I took too long to type). If you go along the coast, Tarquinia for lunch and to see the Etruscan tombs might be a nice stop, if you are going to the west side of Rome or to the airport to drop the car.

Sounds like you know the lay of the land, but you might want to scope out the drop-off point before deciding to come from the east or west.
It is such a pain to have to worry about luggage in the car, but it is what it is! I have not yet decided if it is better to do that in a tiny town or a small city.
I also adore Pitigliano and vicinity.

Years ago we picked up my mother at FCO and then drove or Orvieto for lunch so she could see the Cathedral on our way to Florence for a week. Orvieto was a good stop and it has big parking lots with escalators to the town center. We also stopped in Lucignano to just show her where we had spent the previous week and it was also a nice stop and of course a small town which can be pleasant.

Orvieto is a great place to visit and depending on your car rental vendor, you may be able to drop your rental car there and ride the train into Rome. In addition, the train station does have luggage storage facilities so you can store your luggage while you explore. I've dropped off Hertz rentals there quite often in years past. Also, it's not quite "on-the-way," but Civita di Bagnoregio is only 30-35 minutes from Orvieto.

Siena would be my first choice but is closer to your starting point than you might like.
Orvieto would be second choice and is closer to half way.

As mentioned above, best case drop the rental car in Orvieto and train from their to Rome as you surely don't need/want the car in Rome.

Keep in mind you need a few hours and likely won't want to leave that soon to quickly see one of these towns and have lunch while there. Everything takes time when you have to park outside the city and walk around. You are not going to drive to your lunch location in either case so will not be able to view your car while eating.
I highly recommend stopping as long as you have that whole day devoted to that plan. Even mid afternoon Rome arrival would be tough with one of these stops.

With less time, a smaller town like Montepulciano or Pienza could make sense?

The routing to Pienza takes longer but similar mileage wise, just a more scenic drive and that is the most beautiful part of Tuscany IMO that you would be driving through.

Be aware you are taking some risk leaving luggage in your parked vehicle anywhere in Italy.

siena is a lovely place to wonder around and have a meal

Jean, I'd stop in Montepulciano, and eat here -
https://www.caffepoliziano.it/

there's parking outside of the gate, it's probably a quarter mile walk uphill. It may be the most beautiful restaurant I've ever seen. Unfortunately, we didn't eat here. There's a public bus that comes by every 20 minutes or so. The town is so lovely, a good place to stop.