I’ve read more than a few times that above 35-40mph aerodynamic drag accounts for as much as 85% of the power needed to reach and maintain a given speed: just for grins let’s say you’re using 100hp to drive your truck 100mph, it takes up to 85 of that 100hp just to overcome aero drag. With the brick-like cross section of a squarebody truck, this sounds reasonable. First, get it out of the wind - lower the entire body as much as possible. Next, block off any front section you can, with the intent of making it as flush as you can. It sounds counterproductive, but shoot for a front end that’s flat as a board (not pretty but blocking off sections behind the grille just creates air pockets that eat power and slow you down)
Try to block as much airstream from going under the truck as possible - air dam, spoiler, etc., and yes belly pans may help. Basically, any way to smooth the flow of air over, around or under the truck has the benefits of using less grunt and less gas.
More radical? Keep tires out of the airstream as well, since they create drag and turbulence that disrupt the flow of air over the body. Go crazy and fender-skirt the wheel wells!
I’ve seen different opinions about tonneau covers, but as far as gate-up or gate-down (or removed) it’s been shown gate-up is less drag.
Of course, a smoother front end would certainly lower drag and combined with any other of these suggestions you’d be a long way down the road - so to speak.