Interstates were designed to get you across country as fast as possible, but also to connect the major cities. But US designated highways, while usually very good highways, also typically go thru the middle of every town in route with the slow speed limits and traffic lights. So it takes planning to avoid the cities while maximizing the interstates for speed. There are endless possibilities for getting from Biloxi to Dubois. So here is mine.
From Biloxi I-10 to I-49 using I-12 to bypass New Orleans. I-49 up to I-20, then west on I-20 to US 69 at Lindale/Tyler, TX. North on US 69 to US 82, then west to I-35 at Gainsville, TX. US 69 and 82 are good highways, mostly rural, with a few small towns, but you can make pretty good time.
Then I-35 north to Wichita, KS (short stretch of toll road in KS). You will go thru OKC, but not bad if not during rush hour. At Wichita hit I-135 north to Salina, KS and continue on US 81 to I-80.
I-80 west thru Cheyenne, WY to US 287 and north to Dubois.
This route maximizes the use of interstates and still misses all major cities except OKC. Not bad for that long of a route.
But sometimes you can spend a lot of extra travel time trying to miss just a few miles of traffic when you would be better off just to tough it out for that short stretch.