I have written the first draft of my ms (as described in my profile). It of necessity combines several genres. 1 It is a historical novel spanning 1676 -1745. 2 It is a fantasy novel told from the pov of Jonathan Swift's real life animals. 3 It is a political thriller addressing the politics behind the end of the Stuart Dynasty and the military extinguishing of Louis the Sun King. 4 It is a reinterpretation of Gulliver's Travels to reflect the true personal lives of many of its satirical characters.
The question is this: altho it all hangs together since it is based on the events of Gullivers Travels, will an editor baulk at the mix of genres?
Probably...
But I think they are having to learn to baulk and then look past it more and more. Years ago, genres were very fixed and if it didn't fit in any particular section of the bookshop, it didn't get published. I like to think that's beginning to change. You might want to consider how it might be sold in your pitch to tradition publishers or your own promotional material if you are going it alone. Who will it appeal to and what would they most like to see emphasised on the jacket? I personally think you can throw politics into anything, but if you advertise it's there, you may find your audience limited.
I would think very hard about the purpose of the novel and bring that to the fore when you talk about it, playing down the multi-genre issue which might make it hard to sell.