Actually, there's a lot of it that's much better than guesswork. A classic example of that is the Type 1a supernova — it turns out that once you understand the mechanism of the type 1a, it's possible to know the intrinsic brightness of any type 1a with quite reasonable precision, and it has a particular optical signature which makes it possible to unambiguously identify type 1a supernovae even in distant galaxies. Those two factors together enable it to be used as a standard candle, and knowing the intrinsic brightness and the and the apparent magnitude of one, you can calculate its distance quite closely. (This incidentally serves as a nice cross-check against the Hubble red-shift, just like bristlecone pine tree-ring dating has been used to cross-check and calibrate carbon-dating.) So then if you know how far away another galaxy is by using type 1a supernovae within it as standard reference candles, you can calculate the intrinsic brightness of other events within it, and everything cascades into a big series of "If we know A and B, we know C, and from that we know D ..."
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So then if you know how far away another galaxy is by using type 1a supernovae within it as standard reference candles, you can calculate the intrinsic brightness of other events within it, and everything cascades into a big series of "If we know A and B, we know C, and from that we know D ..."