Thoughts on driving to destination from Rome airport?

I think it is probably not a good idea directly after an international flight but otherwise looks to be all highway so should not be an issue for you. You should be able to stay far enough South of the city center.
Main fear of driving in Italy for me is the crowded city areas Rome that is where driving gets a bit crazy, so take a route that goes around the city to avoid these type of issues and traffic as well. Highways and small town driving here or there are not much different.

Gloria:
I thought we discussed this already (see below).
You can drive from Rome or also take a train to Foggia and rent from Foggia. There is Europcar, Hertz and Avis near the Foggia station.
If you are traveling on a Sunday those locations are probably closed, therefore your only option might be the Rome airport (Ciampino is better if you go south) or the Termini Station. Airport and Termini station are the only options open on Sunday.

https://community.ricksteves.com/travel-forum/italy/renting-a-car-41fc89e0-a89f-4660-8061-a60e2407576b

Roberto,
Yes, you are right, this was discussed before in another post. But that is when I was at the start of planning my trip. Since then plans have seemed to fall in place after many inquires on this forum. I will be renting a car at the Rome airport and drive to Celenza Val Forte. Foggia is east of my destination and would not be feasible to drive beyond my destination.
There are no car rental agencies near my destination. Although they do have buses that go from the train station in Campobasso to Celenza. I do need transportation as the hotel in Celenza is not within walking distance to the town.

After my trip to Celenza I will drive back to Rome airport where I will meet up with my friend and then we both will head to the hotel prior to our Rick Steves tour.

Thanks to everyone for the help they have given me!

I highly recommend you take a GPS with an SD card with maps of Italy. We bought a new Garmin Nuvi and the maps card. Before we left the States, I sat down saved all our destinations. When we picked up our car in the Rome airport, I mounted it on the windscreen, turned it on, selected our first destination and the Garmin took us directly to it!

The Garmin successfully navigated us to every location during our stay. It even showed the road speed limits, which I always confirmed with road signs.

I'm not sure how much you are able to rest on trans-Atlantic flights. We were able to get a fair amount of sleep (we were able to upgrade to first class with our accumulated SkyMiles). We arrived mid-morning and were on the road by 10:30. We took it easy driving to Tuscany and arrived at our agriturismo at 4:00. A check of Google maps shows your drive to be 3 1/2- 4 hours, which would be manageable. The good news is that you can stay well south of the heart of Rome, driving on major multi-lane roads until you are away from crowded areas.

consider taking a local train out of the center of Rome and renting. Many of the train stations have rental car places nearby. It might be easier to get beyond the congestion to start driving. We turned in our car on the way into Rome from the North and it worked well. We rented a portable wifi with the car and google maps were absolutely key for navigation. I did enjoy the countryside driving but would have been pretty stressed trying to drive inside Rome. Remember that most rentals are manual transmission.

Just a thought - driving jetlagged and sleep-deprived is equivalent to DUI. . . . in an unfamiliar car on unfamiliar roads with signage in a foreign language and Italian drivers. Not that there's anything wrong with them, but drivers in other countries are not like most American drivers. If you're used to driving in New York, you may be fine. If you are used to driving in California, it's a lot different.

Are you sure you want to drive the same day you arrive? Jet lag, lack of sleep, and not being familiar with the local road system can all be a problem. There are some people that are not bothered by any of those things. Others think they are ok but are really driving somewhat impaired. Still others are complete zombies and should never drive the same day. Don't mean to rain on your parade, just something to think about.

I appreciate your concern. I do sleep very well on a plane and the location I will be going to is not heavy populate with traffic. So I think I should do fine. I rented a car and they with a GPS system. I am use to driving cross county here in the US leaving for my destination very early in the morning.

I will reply to this message when I reach my destination and let you all know how this first time driver made it!

More on this subject. I rented an automatic from the airport and plotted my drive which will not take me into Rome. I speak some Italian so I don't think reading the road signs will be a problem. At least I hope not! I will have a GPS system that I rented and it will be mailed here to my house. Then I can program in my destination.

This forum is great as everyone gives so much advice!

Watch your speed on the autostrada, especially if you are a bit fogged from the flight. If you are not aware of the Tutor speed camera system it would worth a lot of your spare cash saved to become familiar.

Got your IDP? And know about the dreaded ZTLs?

Remember that car insurance in Italy is different than in most countries.

I wouldn't discount the feasibility of landing and driving. My wife and I have taken a dozen or so trips to various European destinations and always land, rent and go. Most East coast trips leave around dinner time and arrive in the AM.
If you can sleep on the plane, you should wake up ready to go.
I cannot sleep on the flight for the excitement, so driving the first day helps me sleep well my first night in country and dispatch any jet lag.
Not sure if what works for me will work for you, just know it's do-able.
Enjoy the trip

We are leaving for Rome tomorrow, first time in Rome driving. However on sunday we are heading to Umbria and also Tuscany.After driving in April in Milan and all around Italy with a GPS I have no ill feelings and I am not concerned. Do be careful with the speed traps that not only see if you speed but calculate the overall speed from point a to b...very sneaky lol And remember tolls are abound in Italy and its not cheap. They take cash or CC. Enjoy your time , I know we will as well.