You can do some things to increase your fuel mileage. But as I have discovered the past 13 years with my 2007, there is no one item that will give you another 4mpg. However, (1) one of the best mods I did was flat wheel covers, like the discs you'd see on the old Moon Eyes racers. I made a set from corrugated plastic, and cut slots to hold them on the wheel spokes with double-sided velcro straps. The wheel covers alone are worth a 5% mpg increase. My truck gets 20 mpg highway, so that's another 1 mpg.
(2) I made a splitter to extend out from the lower edge of the front bumper plastic. Working on my 3rd version. This one is 3 layers of 1/8" ABS plastic welded together. Previous versions ended up breaking apart. Made brackets extending from the bumper mounts. Can't really claim any mpg, but it combined with the panels helps the truck handle crosswinds a lot better. And keeps the underside cleaner.
(3) My truck is also covered from the front bumper to almost the rear axle, with panels. Brackets all pick up either OEM holes or bolts--I did not want to go drilling holes all over. I had to remove the panels in front of the rear axle to get new tires installed, and haven't put them back on yet. Popular Mechanics did a test decades back where they covered the gap between the body and the frame rails, but I don't recall the exact mpg increase. I can't find the article (or was it Popular Science?)
(4) I fabricated panels to cover the front 2/3 of the gap between the front tires and the body. Back (trailing) 1/3 is still open to let air flow out.
(5) I can find 100% gasoline here in OK. That's typically worth a 10% difference in mpg.
E-85, if you can run it, is about a 25-30% mpg hit. I've only run a couple tanks (mine is a flex-fuel). The owner manual saying engine oil must be changed in 3,000 miles is the other reason I don't run E-85 much. Might change my mind if the engine had higher compression (say 10.5 or 11-to-1).
(6) I run a tune. The 87 octane doesn't really impact mpg, but makes it drive better. 91 octane does help mileage, but sometimes I can't keep my foot out because it's also another 20hp.

The Superchips towing tune tends to give another 1-1.5 mpg.
(7) Bed cover or a topper is another big item. This is another 8-10% kind of item. This is another point I picked up for the Popular Mechanics article. My testing over time with a cover vs a topper shows no dramatic difference between the two, other than toppers tend to weigh more, and consequently you'll take an mpg hit from climbing hills.
(8) I run synthetic oils in the engine, tranny, and rear end. Can't really claim any mpg, but I like to worry a bit, so having synthetics helps.

(9) Almost forgot. I did install and ATI under drive super damper. Frees up 8-10hp. Sorry, no mpg claims here. But it makes dropping the hammer more fun!
(10) Magnaflow 12279 muffler, and Flowmaster Y-pipe. Y-pipe did nothing until I removed the bottle neck of the OEM muffler. Couldn't tell you if the newer trucks are better.
(11) made some small fairings that mount in front of the front tires. ABS plastic does not do well below freezing when you hit a parking block. Tried a slightly different shape, with corrugated plastic, but they don't work as well, so I'll be repairing the old ones and re-installing.
(12) Adjust the nut behind the wheel. In other words, adjust your driving habits. You can accelerate a bit slower, and not drive quite so fast and save some fuel.
Like Po said in Ku Fu Panda, there is no [one] secret ingredient. Just a bunch of little things to all work together to increase mpg.
I will upload some pictures to my garage. Hoping they don't get deleted in the next website update.