If you think your overhead is in method calls, check to see that you're not doing anything which invalidates the method cache:

• Assigning type globs
• Assigning functions into the symbol table
• Creating or removing named functions
• Modifying @ISA

Since you're using XS already, you may want to write a short function to instrument PL_sub_generation to see if its changing. Anytime it increments, your cache is invalidated.

New as of 5.9.4, this function is B::sub_generation