A few corrections to Tom and Susan's message below. The "anchorage" at Fort Myers Beach is now a mooring field (with excellent shoreside services). And, the anchorages they discuss at Big Carlos and New Pass, are a bit shallow for real safety. Otherwise, there's LOTS of good advice in this posting.

In our 15 years of cruising the west coast of Fl from Tampa to the Keys you can depend on your WX channel for this area to be 90% accurate daily  (from our experience). You can also play the weather windows by 'hop scotching' down the coast……Ft Myers to Ft Myers Beach buoy with 4 terrific restaurants and services for you at $13 a night.  From there go to an anchorage inside the Big Carlos bridge (5' or less draft) , or even New Pass if your draft is 3.5' or less; followed by Naples(City Docks or private marinas) or the Rookery anchorage between Naples and Marco on the inside route.
On Marco there are anchorages at Factory Bay as well as off the Esplande (check cruise guides) in a terrific protected anchorage setting(power or sail) with dinghy access to shore, a great Winn Dixie to walk to for resupply as well as coffee shops and restaurants, or just relaxing on the hook.  If you want to splurge and spend the boat bucks dock at the Esplande Marina.  If you have time, and depending on your draft, Goodland is a good stop.  Leave Marco and steam south to the [Little] Shark River and anchor before heading to the Keys……Key West or Marathon. For a short day go to Everglades City after Marco and anchor to port well before the city, or tie up at the Rod and Gun Club in Everglade City.
Regards, Tom & Susan
m/v 'Marbles'