I agree with the above replies. Just go from SFO to MXP with whatever airline has the cheapest price and fastest route (which will probably be changing in Europe rather than in the US, as Roberto says). Once you're settled in Varese, you can then take all the trains you and your children want or need. But I wouldn't want to do that on arrival, so flying to Zurich, even though nonstop, would not be as good as connecting to MXP. Remember that when you connect planes all on one ticket, the airline transfers the checked luggage, so all you have to wrangle through the connecting airport is the children and the carry-ons (which will be plenty). But if you go from a plane to a train, YOU have to wrangle everything yourself.
For comparison, I recently took an Amtrak train from New York to Philadelphia, then a local SEPTA train from the station to the airport, then a flight from Philadelphia to Rome. I did this because the flight ticket cost half the miles that a New York to Rome ticket would. And this went fine. But I was traveling alone and could handle all my luggage myself. Also, I have traveled through these train stations many times, knew where to find everything in them (including bathrooms and elevators), and knew alternate routes (if, say, either Amtrak or Septa were on strike). Having just done this, there's NO WAY I'd try it with a 1 year old and a 5 year old, even to save some money.
EDIT: I was cross-posting with Nigel, and had a similar thought. The California Zephyr from San Francisco to Chicago is supposed to be spectacular (2 nights, 3 days), then you take the Lake Shore Limited from Chicago to New York (overnight). With a family sleeping compartment, it won't be cheap, but all meals on the train are then included. I want to do this trip someday myself, when I have 4 days to cross the country, as well as the requisite funds. If you're interested, here's some more, from The Man In Seat 61: http://www.seat61.com/UnitedStates.htm#Crossing%20the%20USA%20by%20train