I'm only on the fourth mission at the moment, but I can tell you all one thing:
This is by far one of the most unfair "hardest difficulty" achievements I've ever encountered, and I haven't even seen the worst of it yet, I'm sure.
For one thing, the enemies hit like trucks. Second, they FOLLOW YOU everywhere you go. That's right. There's nowhere to run and nowhere to hide. There's no point in taking cover, because every enemy will follow you to the ends of the Earth in a determined effort to take your life. The devs designed the AI for one singular purpose: to terminate you with extreme prejudice, and they will risk life and limb to carry out their programming. Third, the enemies move like MLG pro players. They are ridiculously overtuned here. I've been gaming for many moons now, and I have NEVER seen AI that act as if they need a barrel of Ritalin to calm down like they do here. They will juke, two step, shuffle, basically become unhittable moving targets. Absolutely infuriating gameplay design. Fourth, enemies are complete bullet sponges, so expect to mag dump into the most basic enemies only to barely kill them.
Your shield will get destroyed after 4 or 5 hits, which turns this difficulty into a big game of shoot and run. You will spend more time waiting for your shield to recover than you will actually fighting.
Oh and to make things worse, there are long stretches where you fight through tough battles, only to be killed by some bullshit, and the game sends you WAY back, forcing you to repeat 10-15 minute sections at a time.
Just wanted to give you all a warning about what you'll face if you choose to go for this. It's obviously doable, but it's still extremely tough and borderline cheap.
You can play through the entire game on the hardest difficulty with modifiers and still get the achievement. You must beat the campaign on any difficulty first, then you can replay each mission on Real American Hero with any character you want with modifiers on, which will make this a cakewalk. Thanks to Simply DAG for the confirmation.
One caveat....there are three vehicle based missons that don't allow for mods, so just prioritize towers and watch out for road hazards. I did all three legitimately on RAH first try so they're all pretty easy imo.