Under normal conditions, you'll be fine, although I saw accelerated spark plug wear and had to move to Iridium plugs to maintain scheduled intervals. When I scoped my original engine at 460,000 miles cross hashing still looked good. Had a compression check done around 415,000 when an injector failed, and that was all within factory spec.
The big problem is that some safeties are removed. Turning off torque management is really hard on the driveline (I snapped my pinion gear shaft during a WOT 3-to-1 downshift) and can remove engine safeties too. In my case, I tried to limp north with a plugged fuel filter to stay on schedule. Unfortunately the same weekend, my tuner took a bath so I couldn't go back to stock. The low fuel pressure combined with hot weather, a heavy load, and steep hills caused a valve seat to melt. This wouldn't have happened if I could have returned to stock.
That all said... My first tuner was street-oriented not towing oriented. Now I'm running tunes from 5-star, made for towing. I'm not concerned about either breakdown happening again.
EDIT: One more caution... Don't run lower octane than your tune is made for. Unlike the stock programming, it may not adequately compensate for the lower octane. I carry the tuner with me, just in case anything happens on the road that might necessitate going back to stock.