What is the Least Worst Way to Get from Florence to Nice?

So am I understanding you are taking "Significant luggage"? This may be the first problem. Taking carry on only with a personal item makes you more agile and less of a target.
I see no problem taking a 7 hour train with two changes which will allow you just enough time to transfer trains, not like your hanging out in a train station for hours. Just ran a mock up on Rome To Rio, and looks like a train will leave at 7:45 AM and roll into Nice around 2:11Pm (You would need to verify with the actual train website), which looks like a pretty good day to me. We did Paris to Nice by train and it was around 5.5 hours and very relaxing.
If we fly between countries we have found that a normal airline, as opposed to a "cheap flight", is usually not that much more, allows for checked luggage, and delivers you to a more central airport. We flew Florence to Paris on Air France and it was $40 each (2015) for one way.

Train, might seem like a long time to be on train but I assure you it goes faster than you think. I always take the train in Europe, sometimes it is the best part of the trip. Plus, don't be put off by the " oh dear, so much luggage" people. Your luggage, your business.

200 miles apart.

They are 280 miles apart. It's a 5 hours (+ stops) journey by car. You'd be driving on a divided 4 lanes motorway squeezed between the Alps and the Mediterranean sea. Tunnels, viaducts and more tunnels: If you don't want to drive, wait for Bus companies to release the summer schedules. With a little luck, You could be able to take the direct Flixbus bus on a Saturday. In winter it departs every Friday from Florence at 5:50 pm and stops in Nice at 11:15 pm.

Even the best trains take circa 7 hours with two stops/changes

If you depart from Florence CdM station before 8 AM, you can be at Ventimiglia border station in 5 hours. With reserved seats all the way and 1 change at Genova Piazza Principe station. The Ventimiglia- Nice leg is served by local SNCF trains that can't sell out and take less than 1 hour.

there is risk of theft when you have significant luggage.

No, sorry there is almost zero risk.

Unless you carry only Louis Vuitton bags and you suffer from narcolepsy, luggage theft is very rare. For the simple reason that no teen from Eastern Europe is particularly interested in facing prison to resell used clothes worth... 50 Euro? Tourists are not known for riding the trains with Prada bags and Manolo shoes.

Thieves hate running with somebody's suitcases in tow inside camera controlled stations, whereas they love cash, smartphones and tablets that they can hide in 2 sec while walking away with an innocent face.

Take the train
Pack a picnic
Enjoy the ride

There was a thread about the same trip, but in the other direction, recently. And my vote is still for the train. Ground transportation is not that fast in the area since it is far from flat, you are dealing with the Apennines and the southwestern end of the Alps after all.

No personal experience on this route, but...according to rome2rio:

Trains all require 2 changes, the best one (based on my cursory look) leaves at 7:54 am, takes 6 hours, arrives 2:11 pm same day. 2 changes and a LOT of stops. There are other trains, but all are longer/have more changes.

There's a night bus that departs 11:05 pm on Saturday June 17, arrives Nice 4:40 am on Sunday June 18. Cheap. No changing buses in the middle of the night. But you arrive around 5 am, and if your next accommodations doesn't allow a crack-of-dawn check-in, that might not be a fun morning.

Flights do not look wonderful - shortest is 3+ hours (many are 6+ hours, and that doesn't include time at the airports, getting to/from airports, etc.); all have at least one stop. "Significant luggage" might be problematic.

I do not see any great options, so it'll be a tough call. I'd probably be looking at the train. Not awesome, but maybe the least worst way, it would get the job done. Depends on how you define "significant luggage" and how that might impact those "cheap" flights.

Thanks for the quick responses! Yes, I know trains between Europe’s major cities are usually excellent, and indeed a way I like, even love to travel. But, as I said it is at least two, if not three trains to Nice (no Italian trains ones direct to Nice or French train from Nice to Florence). As far as I can see, and not surprisingly given all the stops and changes, it takes from 7-10 hours. On luggage: We are going to be in Europe for three weeks. I am older and need various stuff, and I don’t want to have to do laundry on trip. On repeated trips to Europe, including a Best of Europe RS Tour in 2018 (by bus), I have never regretted having a piece of luggage that is larger than a carry on. I know RS’s philosophy on this and respectfully disagree. Who wants to have to find laundromat, or buy items that one has at home (if one can indeed find them)? In RS’s book on Italy he points to risk of luggage theft on trains especially if one cannot put it on rack near one.

If Rick wrote about big suitcases and not about small backpacks... I am afraid Rick is wrong. Nobody steals used underwear in 2023 when they can take tons of electronic devices and wallets.

Even if I am wrong, Mr. Rick is right and there is a market for used clothes, you could just stand close to your luggage when the train stops.

Or ride the trains with reserved seats I wrote about above. This way you could pick a seat near the luggage aerea. How can thieves bring your suitcases away and get off the train if you remain vigilant?

significant luggage

Meaning a large quantity or really expen$ive stuff?

Are Nice and Florence your only destinations, or can you rearrange your trip to produce a less ugly travel option?

Does changing the day of travel help?

No direct flights that I can find but flying would be my choice
We always check luggage
Too many changes to take the train for me

I have basically done that train ride in reverse and yes it was a long day on the train with two changes, but it wasn’t horrible and I do travel light. I would suggest that you break it up if 7 or so hours is too long to you, and stay somewhere nice in route. Stretch your legs and have a nice dinner, then continue on your way to Nice in the morning.

Thanks David for some very constructive and useful information! No we can't change our trip or dates without huge expense and inconvenience. Car is tempting but ine way expensive with insurance and all plus the challenge of driving in Italy--yes I did in my much younger days. This is what RS has to say about the risk of theft of baggage on Italian trains in the 2022 edtition of his book on Italy: "Italian trains are famous for their thieves. Never leave a bag unattended," et al. and related page 1193.

The train is really fine... There are some nice views, too - less than there used to be due to many new tunnels, but still!
The drive on the coastal motorway takes a lot of focus: narrow lanes, 50-55 mph limit in many stretches. Even without factoring in the high cost, I do not recommend it.

I had started a discussion on this exact subject not long ago ( opposite direction) so I certainly "feel your pain"! Who would think, as you indicated, two popular destinations so difficult to navigate? At first, I was entertaining the thought of a private driver, a drive of 5 hours and you're there - for $1000! Our trip is in October and we are yet to have our transportation in place. That said, I will not let these difficult logistics change our plans. We feel, at our age, this may be our last shot of doing our own thing on our own . . .

Which statistically is the greatest risk, your luggage being stolen on a train, or an airline losing it? I would suggest the airline losing it is far more likely, particularly if a local says that the risk on a train is being overstated.
What figures does RS have, or is that just subjective opinion. Did he have his luggage stolen?
It's up to you to be vigilant, put a unique strap round your luggage- that will make it less attractive as it is easily identifiable. If it's an option travel 1st class on the train where there will be inherently more space.
You're not going to get many views from the coach overnight.
And what would be the real time savings achieved by flying, probably not that much?
I would opt for the train, rather than arriving by coach before 5am.
Sit back and enjoy the ride. Changing twice means you get some fresh air en route.

With his environmental concerns I don't think Rick would opt for a 280 mile flight if he had other options.

if you're concerned, keep your luggage near you in your sight at all times and/or get some cable locks. just be aware that some people think they're being clever by doing this and then can't get off the train in time at their stop.

By train. Traveling by train is easier if you pack light since you will be the one carrying the suitcases up the train car (3 steps) and placing them on the overhead compartment.