For starters, in the quest for EPA numbers, FCA/Stellantis has already done most of the easy things to boost efficiency. Higher engine temperature, low viscosity oil, more transmission gears, for example. So get comfortable with the idea that the low hanging fruit has already been picked, and any gains you make are likely to be small. Having said that -
Yes, less exhaust restriction can help a bit. Headers may help a little, but there's also that big EPA mandated thing called a catalyst. If you want to risk it and the local authorities don't care, you could rip that out and really open the system up. Or there may be aftermarket solutions that achieve the same thing but are actually legal (expect $$$$). And if you go very far, you'll probably need a custom engine tune (more $$$$) to take advantage of it. And expect tiny results.
A custom transmission tune with lower shift points and less tendency to downshift might keep the engine in a more efficient low speed/high throttle range, but you probably won't like the way it drives.
And again, expect tiny results.
Probably the cheapest efficiency improvement you can make is to not use cruise control when towing. Feather the throttle, trying to minimize downshifting. Let it roll a bit downhill, let it slow a bit going uphill. With only a little practice, your foot will make better decisions than the factory cruise, which is programmed to burn as much fuel as necessary to maintain an exact speed.
If you want any really big improvement, do something about that rectangular box you are dragging through the atmosphere. Find out if someone makes a trailer tail or anything that will help the aerodynamics. And of course, reduced weight and slowing down will help a little regardless, but we already knew that, right?
