This show is, I feel 100% safe saying as an avid podcast enjoyer, among the best things podcasting has to offer. If you're interested in any one of the following, you should absolutely give it a try, even if you don't care about the others: sci-fi, comedy, great improv, goofy worldbuilding, or actual play DnD shows (it's not that, but has a similar appeal).
It's a comedy podcast, so the humor is obviously the main draw, and it is incredibly funny. What really makes it special, though, is how all the other elements are also solidly executed and always manage to support the comedy without ever being sacrificed to it. The characters are charming and goofy and get to have some genuinely sweet moments with one another and undergo just enough character development to make them feel real (despite how outlandish they are). The sound design is incredibly solid and immersive and packed with little details that make re-listening a delight and enhance the jokes, but it's tasteful and never in your face. The worldbuilding is more consistent than an improv podcast should have any right to be, and as characters and concepts and locations get brought back, they double as running jokes and help the world feel lived-in. The plot isn't heavy, but everything that feels like it should pay off does. The humor is often referential but never inaccessible.
Maybe most importantly, the main cast has absolutely incredible chemistry with one another, and it seeps through into every aspect of the show. It's impossible to not have a great time listening because everyone involved sounds like they're having a blast 100% of the time. The guests are also very solid and funny.
I'm also trying to think of a bad episode, and I'm coming up with nothing. Zyxx at its worst is pretty funny. There are a hundred episodes, and my least favorite I would rank a 6 out of 10 (with the caveat that it still got at least three audible chuckles out of me). That is statistically improbable. It's like whichever god is in charge of karma forgot to balance it out with a few stinkers.
A gem of a podcast. I hate to think that I could have lived a life where I never listened to it, and I'm very glad that I did.