When is best time to get a rental car? Traveling from Rome to Dolomites and flying out of Venice

You will not need (or want) a car while in Rome, Florence, and of course Venice. A car is useful (actually necessary in my opinion), for rural/mountain localities like Tuscany (Montepulciano) and Dolomites.
Unfortunately Montepulciano is sort of half way between Rome and Florence, therefore if you rent it after visiting Florence, you will need to backtrack south to Montepulciano before heading back north to the Dolomites. Given your itinerary, in spite of the back tracking, it might still be the best option. The alternative could be to rent in Rome, then visit Montepulciano before going to Florence. But then in Florence (after Montepulciano) you would need to keep the car to gather dust in a garage (or at your hotel if your hotel offers that option). You could also rent a car in Rome, travel to Montepulciano, then return the car in Florence. Later you could take the train to a location near the Dolomites (Bolzano, Verona, or Venice), rent another car, and head to the Dolomites, after which you would drive to Venice and return the car upon arrival.
There are no easy solutions, but I listed all the options you have.

Check www.AutoEurope.com for auto rentals . AutoEurope cuts the rates of the big car agencies and represents many of them. Take an Italo or high-speed Trenitalia train from Rome to Florence. When you’re ready to leave Florence pick up your car at the airport outside of town or in Siena— where AutoEurope has car rental locations it works with. Express buses between Florence and Siena take 75 minutes.
After picking up the car and visiting Montepulciano and Tuscany, it’s a 4-hour drive up to Bolzano— the gateway to Ortisei, Castelrotto and Val Gardena.

When you’re leaving Tyrol and the Dolomites. return the car in Bolzano, Venice’s airport or another town on the way such as Verona or Padua. Padua is about 25 miles from Venice and a 45- minute bus ride to VCE. airport.
Pricing a car out of Florence Airport to Venice Airport on the AutoEurope for 5 days in June 2025 was $474 including all auto insurance coverages and the $55 one-way drop off fee that applies.
Have a great trip!

When you return the car in Venice I suggest you return it at PIAZZALE ROMA, right in the Grand Canal.

That could be fun, but it might invalidate the $0 CDW.

Thank you for the advice.