Handheld tuners or programmers come with generic tunes that you can tweak. Chips don't. The vendors and tuners have tunes already available for almost all combinations of mods out there. Just tell them what car you have and what mods you have and you'll get a tune tailored for your car. But since all cars are different, the handheld programmer will let you tweak the tune even more. Or you can start with the factory tune and tweak that. There are a bunch of parameters that you can adjust [+] or [-] to a certain extent. You can use a dyno to help with tweaking, but this is not required.
If you have major mods that requires tuning beyond the capabilities of the handheld tuner, you can contact the vendor or distributor or tuner and they can get you another "custom" tune that you can load via your programmer. Then you can start the tweaking all over again.
It's like buying a suit. You get a generic size based on your body and then tailor it to your specific needs. You can tailor it again and again as you gain weight. At some point, you won't be able to tailor the suit to the extent that you need. You'll need a new suit, which you can get from the store. Then you can tweak that new suit as you gain even more weight.
With a chip, you basically get a generic "custom" tune from the tuner shop and you are stuck with it. You can not tweak it on your own. Most tuner shops will continue to tweak it for you. Some will tweak it based on dyno runs. Some will tweak it based on what you tell them. Some will charge you each time. Some won't. If the shop is not local, then you'll be FedEx's best customer until you decided on not doing any more mods and have tuned your car to your liking.
Also, a chip is highly visible and detectable by the warranty nazi's at Ford. A flash tune is hard to detect.
That's my summary. Someone else chime in.