A tune will adjust several parameters on the truck such as, shift points, timing, toque management, fuel tables, afm (v4 mode) and such. These can be fine tuned to give the truck more performance and better drivability. The factory tune on these trucks is pretty conservative and really favors fuel economy, sacrificing overall performance.
The handheld tuners as they are referred to on here, Diablo, Hypertech, Superchips, Bully Dog, all adjust several of these parameters in your truck. The problem most find with these is that its a general tune designed to work for several vehicles so performance gains can be hit or miss.. Some like Diablo and Hypertech are pretty popular on here and seem to have favorable results.
However, there are tuners like Blackbear performance that use a software called EFI Live. This is one of the best tuning softwares out there and is also used to tune practically any kind of vehicle that uses obd 2. Blackbear will specifically make a tune for your vehicle either by dyno testing or using a log created by your own vehicles sensors. They will then read this log and see where things can be changed or added, and using your input will create a personal tune for your vehicle. So if you have a headers, a full 3" exhaust, intake and maybe a cam, they can tune your truck to make the post power on these modifications.
Now there are many other people or companies that do this. For example if you go with any of the Diablo tuners a guy called Lew will also do a similar service as Blackbear.