I know of two areas to explore - one is the Ding Darling reserve in Sanibel, and the other (which I've done) is Bucks key off Captiva. There is a canoe/kayak livery in Captiva- Mackenzies, who can provide you with your vessel to get to the flats. There you can pole around searching for tailing reds in the moving water, anchor and walk, whatever...or if nothing is going on for you there you can paddle over to cast toward the mangroves for whatever will hit your clouser - I got a snook on New Year's day doing that. I found sea trout, redfish, lady fish and the snook during afternoons of a family vacation.
I would recommend getting a guide for at least a half day to help you figure out how and what and where exactly you will be fishing. There are fly guides near Sanibel and right at Mackenzies in Captiva...There is also an Orvis shop on the way to the bridge from Ft Myers to Sanibel who will be more than willing to provide flies and the local leader set up. The 8 or 9 weight single hander will be the local choice, but the 7 weight Loop 11'6" was fun for the mighty heave-ho as well.
The trick to the flats is to catch the tides, which are variable.
There are other places to wade that the Orvis shop can point you to. Best luck, Foster