42" Draft is no problem in the ICW (Gulfside, backside, bayside, back country) from Miami to Marathon, then switch to Hawks Channel (Oceanside) for the run to Key West. There is no water for your boat on the backside from 7 mile bridge (Marathon, Moser Channel) West to Key West unless you choose to go all the way to the Gulf which is a waste of time.
The run down Biscayne Bay is straightforward to Featherbeds where you must stay in the channel, then mark to mark to any of several places to switch to Hawks Channel. I would choose to switch at Channel 5 at Islamorada / Lower Matecumbe because the ICW is pretty boring from there West and Hawks Channel is very straightforward.
Cruising the Florida Keys by Capn Frank Pappy is money well spent.