The only type of car where milage can actually improve as a result of a tune itself that I'm aware of is a turbocharged diesel (long been proven on Volkswagens). Otherwise, the only things that will improve fuel economy on a gasser are:
1. Take the "lead" out of your foot (this means speeding as well as rate of acceleration)
2. Learn the art of hypermiling (drafting trucks, pulse & glide driving, turning the engine off at long red lights, etc.)
3. Improve maintenance on the car if your current efforts are shoddy (maintain tire air pressure, make sure air filter is clean, a UIM/LIM cleanout may be needed if you have a Duratec V6, make sure you have good wheel alignment, solve all CEL codes if the car is throwing any, change plugs and wires if worn out, etc.)
4. If tires are due for replacing, get replacements that have low rolling resistance.
These 4 will yield the biggest return on investment.