Advice on our itinerary please!

Need a bit of advice on best way to get from Positano to Tuscany (if we plan on renting a car and driving throughout, is it better to rent in Positano or Rome or on the outskirts of Tuscany??) and recommendations on logistically the best way to do day trips once we get to Tuscany.

Our game plan is 2 nights in Rome, 3 days driving in Tuscany, 3
nights in Positano, and 1 night back in Rome.

Have you checked the distances involved? I'm confused. First you say Tuscany to Positano, then you say Positano to Tuscany. Which is it?

Either way, you don't want to be driving south of Rome in June. My suggestion is to take the train from Positano to Orvieto, then rent a car there.

Have you calculated getting from one region to another in your itinerary? For instance, Positano to Tuscany will take pretty much the entire day. If you didn't calculate that in, then you have 2 days in Tuscany, not 3.

I suggest you stay in an agriturismo near Siena. Based on having three full days, do one day in Siena, one day in San Gimignano/Volterra and one day driving up SR222, the Chiantigiana road as far up as Greve.

If you have not driven in Italy, do your homework, including getting an IDP from your local AAA office. Clearly understand Tudor, remote speed cameras and ZTL's. It's not as hard as some people make it out to be, but you have to know and obey the rules to avoid costly fines.

I apologize for the confusion! Our itinerary is as follows:

Rome (2 nights)
Tuscany (3 nights)
Positano (3 nights)

So I was asking for advice for getting from Rome to Siena, and then eventually Siena to Positano. We were thinking while in Tuscany, setting up base in Siena (like you had mentioned), then a day trip to Florence and then the next day doing a wine tour in the Chianti region. Feasible?

You really need to look at a map. What you are suggesting is not practical. Positano and Tuscany (an area, not a city) are far apart in opposite directions. It should be either Positano or Florence (Tuscany). Difficult to do both without a lot of travel. In some ways it makes more sense to stay in Florence and day trip to Siena, Pisa, etc. Better transportation options.

Second, I would go straight to Florence on arrival and not stay in Rome. Your first day is always shot so waste it on train ride to Florence. Add that day back to Rome. More efficient use of time. You might consider flying to Florence and coming home from Rome. Potentially cheaper with a time savings.

If you are renting a car during all time please note following average driving times:
Roma Airport to Siena 3 hours
Siena to Positano* 6 hours
Positano* to Roma Airport 3 hours
*getting to Positano via Salerno auto way exit or back may take you longer if on a weekend date
These driving tips might help you in your holiday planning or trasportation options