I cut across southern Illinois, Marion, Carbondale, and on east on SR13 to SR3 and up to Chester and cross there. MO SR51 to H to US61 to Z to the interchange on I-55. Fun actually. If you go this way and timing is right, there is Crab Orchard Campground at the Nat Wildlife Refuge at Crab Orchard Lake between Marion and Carbondale. Its all of a quarter mile off the highway. Alternative to that is to cross a little south, Vienna to Anna, and cross at Cape Girardeau.
Crossing at Chester, its the home of Segar, who drew Popeye. Popeye statues all over town, and a Popeye museum of sorts at the east end of the bridge. Fun diversion to keep the trip from being boring but don't waste too much time in the process.
Avoid the US 60/61 bridges below Cairo, they are 20 ft wide, thus 10 ft lanes and I think they have finally banned semis from them, but its not a good way to cross over. I did it just to add to my list of how many ways I have crossed the Mississippi.
Nearing St Louis on 55 take 270 West/North to 64 to 70 then the LONG ride across Missouri, and 435 around KC.
If you want to, go further north to US 36. It is good road from Hannibal to St Joe, almost all 4 lane divided.
Take I-29 north, pretty and smooth ride up the Missouri valley. Consider going west from Nebraska City to Lincoln and taking I-80 west and eventually up to Alliance, Chadron, and Hot Springs, entering the Hills from the south. Actually a few things worth stopping for. The Archway at Kearney, Museum of Military Vehicles at Lexington, Pony Express station at Cozad, or at Gothenburg, Buffalo Bill Ranch state park at North Platte, Car Hinge at Alliance, Museum of the Fur Trade at Chadron (I highly recommend this one), and The Mammoth Site at Hot Springs (I also highly recommend this).
Should you decide to continue north on I-29 to Sioux City and Sioux Falls, just north of Omaha, at US30 town of Missouri Valley, go east slightly less than 5 miles to the Harrison County Historical Village and Iowa Welcome Station. Its fairly large, with several old buildings in the village and lots of stuff in the museum.
At Sioux Falls, exit 79, go east on W 12th Street less than a mile on the right is the USS South Dakota Memorial and museum. Full size outline of the battleship, anchor, a gun barrel, nice museum. Worth an hour or so to visit.
On I-90 westbound at Mitchell is the Corn Palace. At Chamberlain where the Missouri River crosses is about three campgrounds, plus the Akta Lakota Museum and Heritage Center, and up at Ft Thompson at Big Bend dam is the Left Tailrace COE campground. being down in the middle of the Missouri River in this valley is a beautiful experience. It was plan B for me when I saw I would not make the Badlands and the Cedar Campground there. I am glad I got to stay at the COE campground, it was nice.
Charles