If a novel is cross-genre, one of the genres must be the strongest and its genre tropes and plot must drive the novel throughout.
A sf romance is first and foremost a romance. Linnea Sinclair's sf romance novels are driven forward by the romance. Catherine Asaro's novels are science fiction novels with a romantic element. The science fiction plot and worldbuilding drive the novel forward, not the romance.
A werewolf novel that is driven forward by the worldbuilding and various werewolf political/pack struggles is urban fantasy. A werewolf novel where boy wolf meets girl vampire, and they fall in love during various werewolf political/pack struggles is a paranormal romance.
The important thing to pull out of this is that you must understand what the central genre of your novel is so your novel doesn't fail by genre standards.
When you are writing your book, staying within genre or subgenre expectations makes the book much easier to sell to the big publishers in NY.
If you write what you want to write outside of those expectations, you are more likely to have a book that will only sell to smaller markets like an ebook publisher.
You will also have a harder time finding the right readers for your novel.