I once contemplated running a campaign in sort of a reverse scenario inspired by the Dragonstar RPG.
My idea was to run the first few levels of the campaign as a straight-up D&D game with the players none the wiser. Build characters using the PHB and run a series of adventures that way. Then, seemingly out of nowhere, their world is suddenly descended upon by massive floating islands (starships) and at that point, they would be thrust into the "reality" that their world is just one planet in a galaxy full of more advanced beings. I thought it sounded fun.
That said, you might want to consult the Dragonstar books for ideas on how to mesh sci-fi with fantasy. Any edition of Gamma World would also probably give some good ideas.
HARRY DRESDEN — WIZARD
Lost items found. Paranormal Investigations.
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