One big challenge is the sweet spot between flexibility and optimizability. Perl 6 is designed for extensibility, and yet we know at compile time where a given subroutine will dispatch to.

Getting the right trade-offs there was no easy task.

Another challenge was how to make the type system and built-in types so that stuff works intuitively for a Perl programmer, and still has sane rules in the type system.

Finally a thing that's surprisingly tricky is precompilation. You need to serialize types and objects, and then another compilation unit comes, and needs to modify something, so it claims ownership over a piece of serialized data or code. There are way too many nasty corner cases in that area.