My guitar is currently set up with .10-.46 D'Addario's, but was thinking of getting some slightly heavier strings. Will my guitar need to be set up again, or can I just throw them on as is?
If you go heavier or lighter, you'll need to set up string height, truss rod, and intonation, as well as pickup height if you wish.
Need is only if you notice what the differences are, honestly. The intonation is going to be off and the neck may move a bit, but it's not necessarily going to need adjustment.

Yes, it should be setup, but don't avoid trying different strings because you think you would be required to get a setup. You may hate the gauge, then you would need another setup to go back. I have had guitars go stupid from a gauge change and others that never changed a bit other than intonation being slightly off.