Upcoming Italy Trip May-June

Buy the skip the line ticket for Vatican and St. Peters; we paid 50 euros; 150 per person seems like overkill not unless you have the place all to yourself and they give you breakfast. Six days in Siena seems too much to me as it is going to be a human traffic jam there
at times just to get in and out but that is enough to explore the region

I haven't been to the Vatican Museums recently, but from reports of those who have, it seems that you really need to take one of the early-access tours that get you into the museums (including the Sistine Chapel) before the regular opening time.

Just to clarify - Siena is our home base so we can do day trip to Assisi, Florence, Montalcino, and other areas in the Tuscany region that we can get to by bus since we will not drive a car. We plan to be in sight see Siena for one day but we will return each night since we've rented an Airbnb for 6 nights.

Maria

Agree Pristine Sistine Tour of Vatican. Early start, they started at a coffee shop with excellent coffee and donuts( you buy) if you arrive a few minutes early. They put you in groups there before walking over to the entrance where you will see other early tour groups aside from this tour company. Stood a long time before going in, they spent the time telling us about the art and history. One person in a different group passed out, an elderly person. The employees were very fast to react and had the Vatican emergency crew there in moments. With an early tour you will be much better off, but you won't be alone in there. We went through the chapel twice, the second time much later and much more crowded than the first. Incredible art, I had not fully expected the depth and quality of artwork until I was in there. Staggeringly beautiful.
We also spent 6 days in Siena last May so that we could both enjoy Siena fully and day trip to nearby towns. We felt Assisi was a bit too far to drive, so instead went to Arrezzo and found a beautiful town then up to Anghiari, again a beautiful place. It was a quick drive there from Arrezzo. I am now planning our third trip this spring and plan to stay in Orvieto 1 week and will catch Assisi this time. We were suppose to go to Spain this time but just couldn't. Had to go back to Italy, again.

Only other tour I found great was the Gates of Heaven Tour of the Siena Cathedral. This was my second visit there. Loved the tour and the views from the top outside. But favorite was the Picolomini Library.

I'm pleasantly surprised to see that Flixbus has service between Siena and Assisi. The train really wouldn't work for a day-trip; the only train routing that takes less than 4 hours one-way is an afternoon departure (Mon-Sat) that doesn't get you to Assisi until after 4:30 PM, and even that one takes 3 hr. 20 min. The fastest useful departure takes 4 hr. 41 min.

You'll need to stay on top of the bus situation. Perhaps more trips will show up on the schedule later. What I see now is one trip a day, and not every day. The problem is likely that Assisi is in Umbria, not Tuscany. Bus service tends to be quite regional.