I had two F150s with the 4.6. A 97 4x2 and a 99 4x4.
The 97 averaged 17.5 mpg, and would turn in over 20 mpg pretty easily on the highway. It had 3.08 gears.
The '99 averaged 15.5 mpg, and could not hit 20 mpg to save its life. Exact same truck, just different gearing (3.55) and 4x4 drivetrain. Same tire size and body configuration. Literally handed in the build sheet from the 97 and said I want this but in a 4x4.
Most bulletproof engine I've ever run. Did its job without complaint. Heavy loads as mentioned were a lot of higher rev running, but the engine never complained.