Getting from Tuscany to Ortesei near the Dolomites

Flying from Florence to Venice can be done only if you have a lay over in Paris, France or in Germany or in Amsterdam or in Zurich, as there are no non stop flights from FLR to VCE.

You could of course take the train, but why would you return the car in Florence, take the train to Venice or Verona, then rent another car for the Dolomites? That is crazy.

If you plan to stay in Ortisei without a car, then you can take a train from Florence to Bolzano or Chiusa, then a bus from there to Ortisei. From Ortisei to Milan or Venice airport take the bus back to Bolzano and then the train from there to your intended destination. Obviously a car at the Dolomites is useful depending on where you plan to go, and a car offers more flexibility and freedom, and also convenience if you have plenty of luggage, but that is up to you.

But if you plan to have a car in the Dolomites, bite the bullet and drive the 6 hours from Tuscany. It's not that bad. I've done it many times. Just stop at any Autogrill restaurants at any Stazione di Servizio (rest area) along the freeway and take a bio rest every couple of hours. It's almost all freeway driving. I'm sure if you are in America you have taken trips of 6 hours on US interstates.

Take Trenitalia from Florence to Bolzano (via Bologna and Verona; approx. 3hr, 12min). From Bolzano you can take the bus to Ortisei.
Search this forum for the bus details. We did this route two years ago, but I don't remember the details of the bus number. The ride from Bolzano to Ortisei was about 1 hour. For the return, take the bus to Bolzano, then the train to Milan via Verona (about 2hours, I think). We loved the Dolomites and Ortisei (we were there in early June--the weather was perfect, mild in the day, a bit chilly at night).
I hate driving, so bus and train is my first choice.

https://www.suedtirol.info/en/en This the main South Tirol website. It has lots of information.

The bus station in Bolzano is 50m north of the train station so, as already mentioned, take a train to Bolzano and take the bus to Ortisei (about an hour bus ride). Your hotel in Ortisii will give you a free local bus pass to get around in the area. Gillian Price has excellent hiking guides to the Dolomites. If you go in the summer you can take local buses from Ortisei east over the Grodner Joch to Corvara and then the Cortina Express bus to Cortina d'Ampezzo and then the next Cortina Express bus to Venice. In the winter you need to go back to Bolzano and then to Verona and on to Venice of Milan.

I concur that it is totally fine to take public transit all the way. Then, you will avoid long drives and hectic traffic/parking situations in the Dolomites. I visited this region during Covid (with entry restrictions) and parking/traffic was crazy. Parking lots are small and often full from dawn to dusk.

The website for the integrated public transport system in Sudtirol is here:
https://www.suedtirolmobil.info/en#/

You can just enter the street address of your hotel there, and it will tell you how to get there.
Direct trains run from Firenze to Bozen every two hours.

For a variety of reasons, I hate riding on a bus. So with that in mind, I opted to take the train from Florence to Ponte Gardena Laion/waidbruck Lajen. From there, I had arranged for a driver/taxi to pick us up and take us to Ortesei. For me, it was worth the extra expense and shorter drive.