I wouldn't be at all surprised if replacing Tk with native calls via Win32::API could make a noticeable speed improvement in your script. I also wouldn't be too surprised if the overhead of Win32::API made (at least parts of) your script slower.

But I consider all of that irrelevent since the shear amount of work involved would seem to be prohibitive to me. (It may not even be possible due to lack of real threading support in Perl, though I doubt that).