Need Help with Itinerary 9 or 10 trip to Italy and would like to fly to Santorini.

Congratulations on your 10th anniversary!
kDid you visit Santorini on your honeymoon?
Just wondering. Once was enough for us with so many other wonderful and much less crowded Greek islands.
If you keep the Cinque Terre in your plans, you can drive there from Milan or Genoa. Others can advise you on taking trains or buses. We always rent cars in Italy with the exception of cities.
Reports about Cinque Terre are that it is packed with mobs of people now. You have five towns to choose from for where to stay. We stayed in Monterosso at Hotel Porto Roca which has a private beach. Something to consider. Great food at the hotel too.
If you decide to drop the Cinque Terre , consider the Italian Lakes instead.
We usually use Milan MXP and Rome FCO airports for Italy depending on flight prices.
Good luck with your planning.

Thanks for the quick feedback, Suki. Yes, we visited Santorini on our honeymoon along with some other islands and the mainland. We really like Santorini, especially the views. We are also hoping that our dates in April are less busy in Cinque Terre and Santorini. We are just hoping to figure a way to fit all these in without it feeling to hectic. Perhaps we do a day trip to CT instead of spending days there.

Unfortunately, shoulder season is disappearing in the popular destinations in Europe, so April will be very crowded. This means that lodging will already be in short supply. Perhaps check availability in your preferred locations; that may determine your itinerary . Good luck and safe travels!

You've only got 8 days in Europe and want to see 4 different places. But just getting to and from SantorinI and to and from CT will eat up most of 2 more days. I think you would be better served by picking only one place in Italy to visit in addition to Santorini. Leave the rest for another time.

Your to and from airport destinations in IT are Genoa, Milan and Rome. There are no nonstop flights between these cities and Santorini so I recommend staying in IT for ten nights. I also suggest flying in and out of Rome and Milan. Flying between TPA and Genoa requires two connections. You can fly from and to TPA and Milan / Rome with one connection. Check airfare in both directions i.e., TPA to ROM and MIL to TPA and vice vs.
There are direct trains between Milano Centrale (Milan’s central station) and Monterosso in the Cinque Terre: https://www.trenitalia.com/en.html but not many.
Traveling between Monterosso and Siena will take 3h 45 and requires two transfers. There are direct buses that run between Siena and Rome but no direct trains (2h 45m).

We are now a bit confused on where to go. It seems from many people that Cinque Terre could be very busy, even in April. I am taking my parents who are not in the greatest age/condition for rugged terrain either. With our timeframe, what is a good itinerary that includes Tuscany and Rome. My wife would really like to spend time in Santorini, but I am not sure how that would work?

I don’t see nonstop flights between Santorini and IT. With nine nights you’re trying to see too much and the more people there are the harder it is. Especially if they’re not as mobile.
Florence deserves three nights, Siena two nights and Rome four nights if you include Vatican City. This will be easier than what you originally planned.