Amsterdam to lake Como itinerary

A bit more information would be helpful:
What is the total duration of your trip?
Do you plan to rent a car upon arrival in Italy?
Ages of your children?

Strasbourg is midway between Amsterdam and Como. The city is a great place to visit sitting on an island in the river Ill. Flipping back and forth it is a Franco-German experience in the Alsace region of France. Seat of the European Union, wonderful boat tour of the city, great cathedral, tasty food, easy day trip to Colmar.

We are probably looking at 3 weeks or so. The kids are 7 and 11 and experienced travelers. We’d rather avoid renting a car but understand that will limit us. We could base ourselves in Milan and find a bus or tour to lake como. I love the Strasbourg suggestion as that has long been on my bucket list.

A car is a hassle around Lake Como. There is excellent transportation all around, both boats and buses. Do NOT stay in Milan to visit Lake Como; the commute is surprisingly long! Milan itself is worth a visit, but not that great with kids, and you could do it as a day trip from your Lake Como base, which could be Varenna for instance.

As for a halfway stop, Strasbourg is a good call, but your initial idea of Luzern was good too! And the kids might prefer Luzern, with its boat rides and fun scenic train rides. I'll throw a third one in: Boppard, in the Upper Middle Rhine Valley a.k.a. "Rhine Gorge". Very picturesque area. But perhaps not far south enough; the train ride to Milan will be very long still.

If you stop in Luzern, the train to Milan usually stops at Como (the city on the south end of Lake Como - not especially desirable as a place to visit but convenient to the whole lake because the lake boats originate or terminate there for easy access to all the lakeside towns and villages) before it gets to Milano Centrale. Why go past and come back?

A car will be of little help and is an albatross at Lake Como. You can see very little (use the boat) and parking is both expensive and not easy to find - most places will not include it.

If you set Google maps to the train settings, it will give you a pretty good idea of the different routes you could take by train. There is a western route that would allow a stop in Paris, or an eastern route that practically goes right by places like Heidelberg, Freiburg, Strasbourg. So, lots of choices for a stopover.