Discovering words from letters in Clojure (Letterpress Solver)
The (distinct (combo/combinations letters %)) looks mighty troublesome to me. I don't know what the complexity function is for combinations offhand, but I'm going to guess it's got a factorial in it. Using distinct around it means that you will hold that entire set of combinations in memory. That's one of those things that works well for small numbers, then falls off a cliff. 

I also think this is one of those kinds of problems that can benefit significantly from memoization if structured properly. (Although memoization creates a cache in memory, so you might want to build your own with a customized cache to avoid blowing the heap. This is pretty easy with core.memoize.)