We went a long way to visit grandparent with our 1y3mo , and the biggest thing is to have a way to keep them occupied and find or create a safe place to let them loose.

Not sure ho to deal with the 4yo yet.

Keep expectations low. You don’t have to take your 1 year old to Disney. Attention span is short, so keep it cheap. They’re fine doing the same things they do at home, but in other places. Anything different is cool. This McDonald’s has a better playground. The giraffes at our zoo are bigger. This library has fluffier chairs. The silde at our playground is higher. Also, you don’t have to take your kids on every vacation. It’s ok to leave them with family or friend to have time away.

Get a tent, hit a campground, then hit up all the nearby stuff that you like to do with the kids.

Nicer but more expensive get a house rental and again, do local things the kids enjoy.

Honestly, a tour of local public playgrounds is wild fun for kids on vacation - at least in my experience.

Keep the ambitions low, lots of play/snack breaks, and try to pick places where kids can be kids.

Camping is a good option if you already have the gear. Science museums are good too because they’re family friendly while usually having stuff for the grown ups.

Find places with good kid friendly areas. Lots of zoos and children’s museums have toddler friendly play areas. I loved have a stroller and big diaper bag it let me carry extra of everything and a kid could nap while the other played which extended our time out.

Lots of cities and towns in the southern US have drop off daycare where you can leave a kid or two for a few hours while parents get a meal or some time together. Many hotels also have a list of babysitters plus there are online sites that pre screen sitters.

We liked to get a bungalow somewhere in a rural area and stay in the same one for the whole duration, so it becomes a base from where you to day trips with the car, which becomes your second base where all the necessary stuff is with you all the time and where the kids can sleep if necessary.

Not moving between hotels removes a lot of stress already. And then don’t try to cramp too many things into a day, it’s just a rural area, you don’t need to see every single tourist attraction there. Instead explore the local area around the bungalow. Find a local playground, look at the local animals, find the local restaurant and convenience store, etc.

The best thing we’ve done is visiting some friends (who also have kids that age) who live out in a rural area. We don’t have to spend as much time wrangling them that way (especially because our friends already had a child-proofed house), and after the kids went to bed, got to play board games and drink bourbon. The first night for our kids tends to be a bit rough, so we bring melatonin as well.

Even then, it’s still kinda stressful. It’s a phase you’re in for a while, I’m mostly resigned to it (and saving my more ambitious plans for when the kids are easier to travel with).

I’m writing this, sitting in a hotel room with the kids as my wife is outside chatting with her family.
Family or friends with can help quite a bit. Just someone there to take up some of the kids attention is really all you’re asking for. If they want to do more than that, that’s good too.
10 mo old is rough. I’d say, plan to be within 15-30 mins of a hotel for most of the trip. A lake/pool seems like a good option.