As a person who has squeezed some decent MPG out of a truck, here’s my two centavos.
I don’t know if it can be done but if it can you will have to do EVERYTHING right. Consider this: Almost every vehicle known that gets a consistent 40+ MPG is a subcompact car, even then most of those are hybrids or little diesels.
If it can be done, it is not to be done with a little coroplast and duct tape. You have to go to war with the road load equation.
First order of business is adjusting the nut behind the wheel. Go to CleanMPG, An authoritative source on fuel economy and hypermiling
and read Wayne’s manifesto on hypermiling. Take it to heart. Adopt not only the techniques but the state of mind he outlines. Whatever you think of Wayne, he has the goods. He could probably squeeze 22 MPG out of an unmodded H2 Hummer. Without closely approximating his driving, 40+ is not in the cards.
If you have to have a truck, start with an S-10. I say an S-10 is preferable not for any qualitative reason but for the sheer practicality. There is all sorts of mod equipment out there for S-10s. For other trucks you will have to get a real good relationship with a fabricator. Early 90s S-10s can be had for a song, and an off-key song at that. The body-on-frame architecture is easy to mod. Many S-10s came with 14 inch wheels, so you can use the most LRR tires available. If possible get a 4x2, manual shift, long bed truck.
Get a 3/5 slam kit and install it. This lowers the ride height 3” in the front and 5” in the rear. More than 3/5 is available but super-slammed sport trucks are not practical on the street or normal roads.
If you are under 6 feet tall, look into getting the top of the cab “chopped.” This is an old an proven lakesters’ trick to reduce frontal area. Not cheap but it works. If you want 40 MPG, you cannot leave any stone unturned.
After slamming and chopping the truck, lose the stock bed. Have a custom bed fabricated, tapering the bed to a boattail in both the plan and elevation views. You should count on reducing wake area to less than 35% of frontal if you want 40+ MPG. Make the bed out of the lightest material you can afford. Only the bottom of the bed needs to be strong. While you are at it, have the rear axle narrowed so you can taper in even more on the plan view. The long bed layout will allow more length for reduction of wake area while keeping flow attached. Aerohead has mountains of information on this.
No way you’ll be able to see out the back of this setup. Design a CCTV system to give you some idea what’s behind/beside you.
Needless to say, you’ll need front and rear wheel skirts and Mooneyes.
You’ll need to swap out the engine and transmission. For an S-10, the best engine is probably a VW TDI, preferably a pumpa duze engine. (Common rail engines are very new and finding one is not likely. An old 4.3 GM diesel would work but good luck finding one. A 4BT3.9 Cummins is too heavy. Get an adapter made to mate the engine to a Tremec T-56. The T-56 has a very wide spread of ratios and its huge 0.5:1 overdrive will allow you to find an axle ratio that will let you run the engine under 1500 RPM at highway speeds.
Get rid of the auxiliaries. Lose the power steering and power brakes. S-10s in stripper form came that way. They are probably the last pickups that could live without PS/PB. Rip out any radio or stereo. No way you can retain an air conditioner and expect 40+ MPG.
Put the truck on a starvation diet. Get the smallest battery that will start you engine, and the smallest alternator that will charge that battery. Rip out all the soundproofing. Rip out all the interior trim.
Leave the brakes alone. S-10s have weenie brakes as is.
Finish off the aero package by covering the belly best you can and replacing the bumper and grille with rounded replacements with minimal openings.
All this is stuff racers have been doing for decades.
Unless you have the physique of Lance Armstrong, go on a diet. If you are like most Americans you should be able to diet off 20 lb. At this point another 20 lb off the truck may be much more difficult than taking it off you.
Get LRR tires. Inflate them rock-hard.
To tell you the truth, the project is not worth it unless:
You are over six feet four inches tall
You absolutely need freight-hauling capability
You want to make a point
If none of those apply, it would be much easier and cheaper to find a woebegone first generation Insight and restore it.
For some the simple challenge of doing it is worth the effort. At that point the truck ceases to be a DIY economy vehicle and becomes a true hot rod.
IMO, a DIY economy effort won’t get to 40 MPG. A true ecomodded hot rod just might.
And I don't believe for a minute an old Dodge with a 12v Cummins will get 40 MPG. I don't believe 27 unless you never drive over 35 MPH.