Key West to Cherokee, NC - Best route suggestions

TCI wrote:
I'm leaning toward I95 to I26 to I40 to I19.

I "assume" you mean US-19. You do not want to take US-19 from I-40 to Cherokee. Instead take US-74 to just south of Cherokee and then US-441 on into Cherokee. US-19 between Cherokee and Maggie Valley has some very steep grades and sharp curves. Tractor trailers are warned not to take that route by several signs. You will find US-74 to be easier for a big rig.