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You can absolutely play them against each other, there's no restriction against worlds. There might be kitchen-table rules where people only want to play within a certain universe, but honestly I've never run into that myself.Alright, I'll try out some more Arena to get a good handle on things.
So about commander decks, are they all playable against each other? Like those third-party sets, I think Doctor Who is the big new one, and there was a LOTR set not too long ago, can you pit those commanders against each other or can you only play within the same franchise?