There is a wealth of good cruising tips in Captain Lloyd’s note below. His description of the “inside” passage navigational challenges, behind Marco Island, is spot on, as is his description of Little Shark River’s shoreline.
I might also add that as of a few months ago, the entrance channel into Flamingo was still quite shallow!
You can take the inside route behind Marco Island with a 4′ draft but avoid low tide. Charted depth is 4′ but depth increases by 3′ at high tide. Pay attention after Bear Point bridge as daymark colors switch sides. A red daymark appears to be out of position but it is not!
Definitely stop at Goodland, an old-time fishing village that is a marked contrast to the rest of Marco Island. Calusa Island Marina is within walking distance of restaurants.
Some boaters recommend Everglades City but I usually go directly from Goodland to Little Shark River in Everglades National Park. This area of the park consists of mangrove Islands and hardwood hammocks, not acres of sawgrass that one usually associates with the Everglades. There is a very protected anchorage about 1.5 miles up river.
I have not been to Flamingo since it was rebuilt after the hurricane. The approach was shallow at that time. I recommend a direct route from Little Shark River to Seven Mile Bridge and stop at Marathon.