[cleanspeed1]

Start with a full tune up and a Scangauge. Learn to drive better and document your mileage. Replace all lubricants with synthetics. There are people on here with pickups that you can get ideas from.

After that, it depends on how far you want to go with it.

Look up aerohead: he has used aero techniques on lots of vehicles with great success.
Probably has the most experience with aerodynamics.

Then you can go into the mechanics. Change the rear axle ratio to something that slows the motor down on the highway if you don't tow or do serious hauling with the truck.

Reprogram the engine computer for better performance and economy.

Really want to get into the guts of the motor, do a cam swap.

But start with the easy stuff and become a better driver.