Where are you staying on Lakes Como and Maggiore? That makes a difference in recommendations on train routes. Your mention of Tirano suggests you are heading to Varenna, so I will assume that in the following discussion.
It is difficult to travel around Switzerland without changing trains one or more times on the way to your destination, unless it is a major city. Just to get to Luzern you will have to change trains at the main Zurich station if you are coming from the airport. And if you want to take the Bernina Express to Tirano, you need to get to Chur, which can involve several more changes.
The Glacier Express will take you to St. Moritz, where you would have to transfer to the Bernina Express to reach Tirano. This is a very long journey and I would not recommend it for your short time in Switzerland.
You can see the various scenic train routes highlighted on this Swiss rail map:
https://www.mystsnet.com/en/download/swiss-travel-system-map-en-2023/?wpdmdl=14294&masterkey=63a023c8da36c
You have several options for your 3 nights in Switzerland that will position you for travel to Varenna. One, suggested above, is to head straight to Luzern and spend your time there, daytrip ping (without luggage) to the sites you want to see. But the travel time to the Bernina Express start is long, and best not done all in the same day that you ride the BE and travel onward to Varenna. That means 2 nights in Luzern, then travel to Pontresina for your 3d overnight.
This plan would involve the following transfers with the luggage: train from Zurich airport to Luzern, 1 hour with a mandatory change at Zurich Hauptbahnhof. Then Luzern to Pontresina, the simplest journey of which takes 4.5 hours and involves 3 train changes.
You can eliminate some of these train changes by heading to Bern instead of Luzern for your first 2 nights. Bern is a lovely little city nestled in a horseshoe bend in the river, with good connections from Zurich, and to the Berner Oberland and to Pontresina.
Like this: Zurich airport to Bern is a journey of just over 1 hour by direct train (no changes). From Bern, you can reach the village of Lauterbrunnen in the Berner Oberland in 1 hour 24 minutes, with a single change on the way (but you will have no luggage here). Easy transfers there to the carfree villages above the valley. Then from Bern to Pontresina for your Bernina Express trip, you have a journey of 4.5 hours with a single change on the way, at Chur.
In total you have eliminated 3 train changes with luggage by spending your nights in Bern instead of Luzern. And this may be heresy here, but we much prefer Bern—-it has a very attractive Oldtown area with far fewer tourists, good hotels, and nice restaurants with outdoor seating lining the (mostly pedestrian) street. On a Friday evening in September the street had a nice celebratory feel, not wild or raucous, just locals enjoying a nice weekend evening together. By contrast, we have yet to find a hotel or a restaurant we really like in Luzern. Now we stay in Weggis, right on the lake, instead.