I think the biggest challenge is compilation time. With the lack of incremental compilation modifying more complex classes can result in long compilation time. Same is true for modifying templates that are widely used within the code base.

If you look for example at runtime compilation of queries in database systems, compiling can take significant amount of time, at least enough so it doesn't feel instant anymore.

To get incremental compilation, one would need fully dynamic dispatched invocation which would be probably horrible slow.

This said, I'm a strong believer in runtime code generation, just with a reduced scope rather than full c++.