Renting cars France and Italy.

Unfortunately, the answer is maybe. You just have to check. Rental cars are available through out Europe but very small towns especially without rail or bus access probably will not have rentals available. Whether they are more expensive will just depend on the market. Generally, but not always, rentals away from major train stations and airports will be less but selection may be limited. And, drop fees will vary depending on location. If you drop in another country the fees will be very high. We have dropped at locations in France for 25 to 50 euro. So far in Italy was zero one time.

Yes, easy to get cars in most big towns. Often there are car rental offices near stations.
Outside cities you may find the offices are business hours only, 9 to 5 and closed on Sundays.
One way car hire is usually possible as long as the company has offices in both your start and end location. But renting in one country and returning in another is usually either not possible or very expensive. Taking the car over the border and returning it back in the origianl country is usually OK.

We've rented a few times in France. We always do a one-way rental. We usually pick up and drop off in "medium" sized cities, like Colmar, Chartres, Tours, etc. I use Autoeurope (a consolidator) and the car usually ends up being from Europcar. We have not had a drop charge. I usually end up calling Autoeurope (English speaking based in the U.S.) to clarify things like drop charges and any local taxes. For my last rental, I was surprised that there was a tax/surcharge at the train station, similar to airport locations so I would ask about that. My rentals in Europe have been less expensive than my rentals in the U.S. I would suggest doing some searches on Autoeurope trying different cities to get an idea of cost.

yes, like Chris said, be mindful of operating hours. Some have fewer hours or are not open on weekends and we've found some that are closed for a bit in the afternoon.

Just beware that rental car companies are often limited to larger cities in any region. The smallest cities are where car dealers are the only source of rental cars, and they don't want them taken to other cities or regions where they'd have to go after them.
And if you're traveling from Italy to France or vice versa, you might want to look on Google Maps to see how far it is between cities. . Distances are greater than you realize in parts of Europe, and very inexpensive budget airlines are often easier to travel on when going very far.

Go to the website for AutoEurope and you can see pick up and drop off locations.

When in Italy, if there is regular train service to a destination on your itinerary, you may want to do what most of the locals do--take the train. This is especially true for urban areas.

We have found rental cars are less expensive in France than Italy and have flown into Nice and driven over to Italy. You don’t want to pick up and drop off cars in different countries. Is Annecy the only place in France you are considering?