Best way to travel from Rome to Switzerland, and spend 7 days touring Switzerland?

Fly into Rome and out of Zurich or vice versa.

Buy the Swiss travel pass 6 day or the Swiss Half fare card. Switzerland trains always run on time through some of the most beautiful mountain terrain in the world. It is not comparable to anywhere. It is worth the steep price
You do not need a pass to ride trains on Italy. Most here will tell you to just buy point to point tickets and you only need to buy high speed long distance train tickets in advance to get the best price around 90 days in advance.

Do you have any plans to see northern Italy? Rome to Switzerland is a long train ride, so I would want to break that up by perhaps stopping in Milan. Or maybe make your first stop in Switzerland Lugano. Do you have any interest in staying in the Berner Oberland? Or maybe Lucerne is more to your liking. It might help to watch the RS videos on Switzerland to see what interests you:

https://www.ricksteves.com/watch-read-listen/video/tv-show/great-swiss-cities

https://www.ricksteves.com/watch-read-listen/video/tv-show/best-of-the-alps

https://www.ricksteves.com/watch-read-listen/video/tv-show/swiss-alps

We have taken the train from Rome to Switzerland many times. We generally go right to Lauterbrunnen in the Berner Oberland, taking a high speed train to Milan, then a EuroCity to Spiez, Switzerland, where we change to the local trains required to get to Lauterbrunnen.

Current schedules show you can leave Rome at 7:20 AM, arrive Milan at 10:35; leave Milan at 11:20, arrive Spiez at 13:53. From there, trains leave every half hour with a change at Interlaken Ost.

There is nothing but scenic beauty and day trips galore in the Berner Oberland. There are easy walks with minimal hills, amazing transportation. A Swiss Half Fare Care plus a Berner Oberland Regional Pass would help with the expensive transportation costs.

If you want a city experience, spend a couple of nights in Luzern before flying home.

Thanks everyone for your helpful ideas! We will take the train from Rome and
spend 2 nights at Lake Como;
3 nights in Wengen -we plan to take the bus down into Interlaken for a day;
3 nights in Lucern - is there enough to do here to keep us busy?
1 night in Zurich

Does that sound like a good plan? Originally I had wanted to spend two nights in Sienna and shorten our Wengen and Lucerne stays, but the train rides and transfers were too long.

At what time would leave your return flight from Zürich? If it's after 10.00, you do not need the last night in Zürich and could thus add a night in Wengen.
And to minimize travel time, I would consider Lake Maggiore over lake Como. You could stay in Stresa, and Stresa to Spiez (for onward connections to Wengen) is a quick (under 2 hrs), direct train ride. That lake is less mountainous than lake Como, but the Borromean islands just off Stresa are simply delightful, and you will have your fair share of mountainous lakes in Switzerland.

3 nights in Lucerne - is there enough to do here to keep us busy?

I was just in Lucerne for 7 nights and never ran out of things to do.

Like balso suggested, I would add a night to Wengen and skip the night in Zurich. The train from Lucerne will take you right into the airport in just over an hour. So, save yourself the hassle of changing hotels.

Agree you should skip a night in Zurich unless necessary for travel. You will have plenty to do in your other destinations and there is so much time lost changing accommodation! Check out older posts about each of the locations for ideas or post again specifically about activities in each one. There is lots of knowledge and experience on this forum!

A few thoughts to add to the other posts.....

A rail pass is rarely a good value in Italy, especially as they don't include the compulsory seat reservations on the express trains. You'd have to buy those separately "out-of-pocket". The reservations are specific to train, date and departure time so can only be used on the one train listed on the ticket. Those caught without a valid reservation for the train they're riding on face hefty fines which are usually paid on the spot!

The question of a rail pass in Switzerland is more complicated. Whether it will be good value or not depends on exactly which rail trips you'll be taking there, so it's often necessary to work out the P-P cost for each trip and then compare that with the cost of the pass (often a daunting task). If you're going to be spending most of your time in the Berner Oberland, the BO Regional Pass may work well for you - https://www.regionalpass-berneroberland.ch/en/ .

There's lots to see in Lucerne so you may want to spend three nights there. You could travel to Mt. Pilatus via boat to Alpnach, the Funicular to the top and then cable car down on the other side and bus back to Lucerne. There's also Mt. Rigi and of course the city of Lucerne. As others have mentioned, you can take the train from Lucerne direct to Zürich airport in just over an hour.

IMO, you may want to skip Lago di Como as that will take time away from your time in Switzerland. Travel to and from Lake Como wiill require about a full day.

Thanks for your helpful replies!.

I have always wanted to see Lake Como, but the rail trip from Como- Milan - Speiz - Interlaken Oest - Wengen takes about 6.5 hrs and involves 4 transfers. Has anyone ever taken this route or have a better suggestion? I thought about renting a car, but picking
up an automatic in Italy and dropping it in Switzerland isn't available.

4 transfers is the minimum, but 2 of those are inevitable no matter where you are coming from. At Interlaken Ost (no umlaut) you go from standard gauge railway to narrow gauge railway with rack-and-pinion assist for steep sections. At Lauterbrunnen, you change to another narrow gauge line for the steep climb up the mountain to Wengen. The curves are so narrow that no more than 3 cars can be coupled together, so they send up 2 or 3 trains at once following each other by about 100 meters. Autos can't get there, so train is the only way.

From the city of Como, you could get there in 5 1/2 hours with changes at Lugano, Luzern, Interlaken Ost, and Lauterbrunnen. The section from Lugano to Luzern includes the longest underground tunnel in the world, 35 miles. While not much scenery as you burrow completely under the Alps, the section from Luzern to Interlaken is quite scenic going over the Brunig pass.

You don't want to rent a car in Italy and drop it in Switzerland because international drop fees will be huge. You can't rent a car in Switzerland with Italian number plates, so the car would have to be transported back to Italy at your expense.

Am I better off staying in Lauterbrunnen vs Interlaken? Which is more centrally located for day trip transportation and walks around town?

Of the two, absolutely Lauterbrunnen!!! It's the transportation hub for the valley, and you can easily and quickly access both sides of the valley from there.

Interlaken is NOT where you want to stay or even spend a day trip. It's mostly tourist shops and not much substance. Lauterbrunnen is a good place to stay, and easy to get around. Go to Thun for the day rather than Interlaken. About 30 minutes by train, and it has the Castle, the Aare River running through town, and is quite charming. Take a riverboat around Lake Thun. The water is stunning.

We will be going from Wengen to Lucerne - stopping in Bern just for the day (hoping to save 1:20 by not back-tracking to Wengen). Is the scenery significantly nicer taking the route from Wengen to Lucerne vs Bern to Lucerne?

Is the Tell Regional Pass worth it - kinda pricey at 190 CHF for just two days. The Berner Oberland Pass is only good for the main train line once in Lucerne.

Thanks to all for your helpful replies.

Wengen to Luzern via Bern is really a round about way, since there is a very direct and scenic route from Interlaken Ost to Luzern. Bern to Luzern is only scenic on the RE train that takes longer than the IR route. The IR route takes 1 hour, going through Zofingen and Sursee. The RE train goes through Langnau and Wolhusen and take 1 1/2 hours.