My parents stayed a few years ago at a really neat little Airbnb in Anna, I think, that was a converted old schoolhouse.

Cairo one of the few places a where a big river meets another where there is no real development.  First Illinoian glacier stopped short of Shawnee, so rough thin ground, lots of forest, the Cache River is kind of an almost southern swamp.  No real roads or strong ag presence on the IL side, just relatively undeveloped.  Don’t know as much about the KY side or MO side.  Good hunting if you know a local.  

I worked in Carbondale for a while and south of Shawnee forest is kind of an Appalachian feel, just hard scrabble ag productivity because of the land resource.  But some cool orchards and there is a wine trail all around Carbondale and south, if you want to go an hour of Cairo north to Walker’s Bluff winery it is or was a passion project of a Silicon Valley type with a really nice ambiance, family friendly, higher end dining experience option as well.

if you are up in Murfeesboro there is 17th street bbq, hole in the wall N Carolina style BBQ.  

Lots to see in Shawnee.  You can end up in Paducah, but if you drive around the forest have a food and gas plan because it is big and sparsely settled.  

You can go over to Cape Girardeau and start getting towards the Delta experience.  You can follow the River road up through the land of Popeye the sailor and it just gets better as you go north, you go through Calhoun county and more orchard and farm stands, and eventually you get all the way north of quad cities and it turns gorgeous.