The really rough rule of thumb is 1800 rpm cruise rpm on the highway (~65 mph) will net you the max fuel economy. This is typically 25 mpg for our trucks, with lower lift and smaller radials.
Every extra 100 rpm at 65 mph loses you approx 1 mpg.
If you start crunching numbers using the online gear calculators you'll soon see how valuable an OD tranny is for these engines. It takes aggressive gearing to get them to where they feel like they make good power, and then OD to keep them in the mpg sweet spot on the highway.
I only drive my '83 to work and back...so the variables are well defined and don't change much if at all. I've been playing with things like tire pressure to see what if any effect it has on my fuel economy. Went from 32 to 37 psi and saw no appreciable difference in economy. Next up is an oil change which it needs anyways, new air filter, and new fuel filters. Exhaust is soon, likely 2.5" or larger duals.
Beyond that the only other stuff i could do is get rid of the huge camper mirrors (95% for sure that's gonna happen) and lower it 2"/4" (95% sure that's not gonna happen

)
It's my rolling 'experiment'...
my guesses before hand. Fuel filters...no gain. Air filter, .5 mpg gain if it's as dirty as I think it is. Camper mirror delete...maybe .5 mpg (they do have a pretty large flat surface area). Oil and filter, no appreciable gain. Lowering it...no gain. Exhaust...possibly a .5 mpg gain. I think this one really depends on how poorly the currect 2.25" duals with turbo mufflers flows.
So I might squeak up to a tick over 25 mpg on my regular drive.
Right now I get 420 miles from one tank, and it takes just over 17 gallons to fill. That's two weeks of driving for me.
Rene