But in a fictional setting, who would the unwelcome guest actually be? In a fantasy/science fiction setting, I think the range is huge. All those species to choose from (and invent!) for a start. There'll be plenty in there to set against each other!
So, as well as working out who the unwelcome person/being is, let your reader see why they're unwelcome. The unwelcome guest has got to make your hero/heroine desperately uncomfortable at the very least and for good reasons. Funnily enough they don't necessarily need to be an enemy. At times friends and family can make you feel uncomfortable (this is the moment you look at yourself in the mirror and honestly face up to why this is! If they're all doing this, the problem is going to be with you!).
How does your leading character handle this situation/person? Can they turn the unwelcome guest into one that is welcome? If your leading character is the one at fault and therefore generating the uncomfortable feelings by their own actions, what do they do to rectify this?