Let me address two points you made in your original post. You plan to use the RV for long cross country trips. As you know from your TT, the slides are no benefit while driving down the road. Only when stopped. Even then, they add some time to set-up and take-down at CGs, and you need to check out the site for trees and other obstructions. No biggie, but still requires the extra steps.
You asked about structural issues. Other than failures to extend or retract (not frequent, but do occur), the issue with slides are their added weight to the chassis. Later model Ford Chassis like the E450, have a GVWR of 14500 pounds. All manufacturers get this much weight to work with when constructing a RV. Generally speaking, the longer the RV, options like leveling jacks and slide outs add weight and take away from the OCCC (Occupant and Cargo Carrying Capacity). So, how much weight you plan to carry may be affected by the slide out. How you plan to use the RV will have some impact on this. For example, going to the same campground only on weekends will require less "stuff" (food, clothes, gear) than spending weeks traveling across the country. So, OCCC may be a consideration.
So, think about how you will use the RV most of the time. Think about the weight of the RV you are considering. Make sure to find out the OCCC of the unit under consideration (do not depend on the sales rep for this info., look for a sticker in the RV). This will help you decide slide or no slide.
Best wishes.