Okay, so the story I'm working on right now (have no idea if I'll ever finish it, as I have serious ADD which makes me give up and start something else halfway through) is an operatic, Greek-tragedyesque fantasy tale, which mostly takes place in an alternate universe, but a good chunk of the first half takes place in our world and has the general tone and style of a high school comedy. My question is: is that a good way to go? If you want, I'll give you further details on my story so you can have a better idea of my problem.
To pull it off you really need to master both genres. Can be done, you didn't give me the impression of someone that have written much. A big setting switch halfway through is hard to pull off too, really hard since you want to have your reader appreciate both setting and have them feel like a meningful unity in the book.
Mixing genre is not a new thing, such as when parallel worlds cross and you end up with a scifi-horror mix, or a fantasy-romance. Mix it up as much as you think is necessary, but keeping it believable and somewhat realistic (according to the basic plot and genre you finally decide on) may be the real conflict you my run into, as long as you feel it is working out the way you want to, then that is the most important thing.