Hi Nate -
Hope you are well.
The Keys can certainly be fished on ones own but of course you will get more shots with a guide. I would look up Ben Iannotta Jr on bigfishonfly in Summerland Key for starters.
I fished the keys four years in a row a while back. I got lucky DIY on big keys bones at Matecumbe and Bahia Honda State Park during these trips but most shots I spooked the fish and felt I was not covering the area well on my own compared to with a guide. I did however land an 8 # fish on my own.
Found mudding fish several occasions along the hiway where parking is available you could fish deep and blind for them in the muds.
My favorite DIY spot was Bahia Honda State Park. Do a search for more, we have posted on the keys on multiple occasions as I recall.
IFFF Certified THCI @ 2005
Capeflyfisher Guide Service
Island Hopper, Guitarist, Incurable Dreamer
and Founder, Worldwide Flyfishing Forum