We are spending 4 nights in Venice after cruise and want to do a trip to Rome. Possible?

Sure it’s doable but how enjoyable or necessary ?

It’s a 4 hour train ride each way
You’ll be paying for double lodging for a very short visit to Rome

Save Rome for another time
Enjoy Venice

I’d do a day to to Padua. It’s a short train ride from Venice. To be truthful, Rome deserves several days.

My quick research finds the earliest train from Venice to Rome arrives Rome at 930AM
The last train from Rome to Venice leaves at 730PM

That gives you 18-20 hrs to run around Rome

If you are content to have a trip that is like 'grazing at Costco', vs a sit down meal at a restaurant, then do it.

Your expectations will determine how enjoyable/worthwhile you find doing such a trip.

I agree with the others that it is too long to travel for such a short time. I suggest an easy trip to Bologna from Venice.

It’s possible to do Rome but I wouldn’t recommend it.

Venice, alone, deserves several days. If you want a side trip, you have many good options such as Verona, Padova, Treviso, Bologna, Ferrara or Ravenna.

Joe, I'll admit that math is not my strong suit but 9:30 AM to 7:30 PM is 10 hours, not 18-20?

Numbers aside, I'm 100% with you on the 'grazing at Costco', vs a sit down meal! Rome wasn't built in a day, and can't be adequately digested in just one. civilag92, save it for when you can give it the time it deserves, and choose a different day trip - much closer to Venice - from some of the excellent suggestions offered up.

I think OP is talking about an overnight rather than a day trip.

The OP said they wanted an overnight trip to Rome, so they would or could have the majority of two days there- thus 18 to 20 useable sightseeing hours is about right.

Would it not be better to leave the big luggage at Venice Santa Lucia station than to pay for a Venice hotel room just to store luggage in?

Even an overnight to Rome doesn’t make a whole lot of sense when there is a rich abundance of stuff that will be right under their noses in the Veneto region. But you are right; I misread the original post.

Rome is amazing but I would save Rome for when you can really see it. You can spend a month in Rome and barely scratch the surface. It all comes down to traveler’s preference, though, and whether this is a once-in-lifetime trip or whether they plan to return somewhere down the line.

What is your flight schedule? It would make more sense to fly home from Rome so you could spend a couple of days in Rome before returning. Check a map. Rome is just too far away from Venice. Or get off the cruise and take a train directly to Rome. Rome is roughly 325 - 350 miles from Venice. Not doable.

DOH!!! Missed the overnight part! Apologies, Joe!
But I still think a closer option would be better.