My experience with my V10, 12,500 pound C motorhome, the best MPG speed will be dependent on wind conditions (but not nearly so much as with an airplane), and it will be slower than you want to travel, likely slower than minimum legal speeds on rural limited access highways.
A device like a Scan Gauge can help you tune this, because it calculates an almost instantaneous (really short term average) MPG. You may not like what it tells you.
For my motorhome, in still air and level ground, best MPG is right where it shifts into overdrive in normal acceleration, and can hold the speed at light throttle. This is usually around 35-40 mph. MPG can be well over 10 MPG, I've seen 12-13 for long periods on the gauge, but it fluctuates a lot with slightest difference in grade, at this low a speed.
With a 10-15 MPH tailwind, I get the same MPG going 10-15 MPH faster. Seldom am I so lucky the wind is almost always against me.
Going into headwinds, more throttle is needed. At too slow a speed, this means a downshift, so to stay in overdrive, the speed might need to be raised to 50-55 mph. This might be a 9-10 mpg speed range in no wind, but might drop to 7-8 in a 10-15 MPH headwind, as if I were trying to drive 65-70.
Running the generator (1/2 gph no matter what speed) or dash A/C (5-10 HP extra load) raises the optimum MPG speed, because you need to cover more miles even though that also costs some fuel. The engine cooling fan is a huge consumer of power, no matter what speed, but fortunately it is usually declutched at highway speeds.
In general, on high speed rural highways, the best speed for MPG you can realistically get will be the slowest speed you can comfortably and safely travel in the traffic environment. This is the reason DOT picks 55 MPH as an economy driving speed, not that 55 is a magic number that works the same for all vehicles.
I've done some of the same tests on my Honda Fit, the optimum speeds are quite a bit higher, probably because the cross-over point for power to overcome drag vs power to run accessories. 5-10 HP to run a small A/C vs 16-20 HP to cruise 55, is a bigger relative factor than 10-15 for A/C against 120-150 HP pushing that big box against the wind.
Tom Test
Itasca Spirit 29B