"What are the facts?"

Translation: Quels sont les faits ?

[sjaques]

Would "Qu'est-ce que sont les faits?" work/be natural?

[Ekalisood]

Using "que" or "qu'", you're asking an absolute question, i.e. what are "facts" in general.
Using "quel" you're asking the question in context and i.e. you ask for the facts specific to the situation you're talking about.

"Quels sont les faits ?" = "What are THE facts?"
"Qu'est-ce que sont les faits?" (or more naturally "Que sont les faits?") = "What are facts (in general)?"

Hope it helps

[Pixies_Debaser]

A good reference for when to use quel(s) /quelle(s) is:
https://www.lawlessfrench.com/grammar/interrogative-adjectives/