I suppose it's because there isn't really one answer.
Look, I don't want to sound like the authority here, as I'm just passing on my own personal experience. In my case, my multi-genre attempt just didn't really work. Looking back, I can see why - I mean, a dark fantasy laced with slapstick comedy? And then wrapped in anti-Biblical myth? It also weaved between fantasy and science fiction rather wildly, and was, all told, a bit of a mess. I can see that now.
In my case, it was a question of someone advising me that in being over-ambitious and wilfully experimental, I'd perhaps created one of the most interesting literary non-sellers they'd ever read - although the writing and the basic plot were great, apparently, so that just made me a pain in the arse. Focus!
JB
<Added>The agent actually told me I was a pain in the arse. That was an eyebrow raiser, I'll tell you.