Thats too big of of question. The basic drawback is that each Tk widget is an entity in it's own world, whereas every widget in a gtk2 is all based on the same object model. This makes it difficult in Tk to get low-level interaction between widgets in an app.

But to just make a list of common complaints about Tk in complex apps...... sorting lists is difficult, memory is not cleaned up very well, getting colors into the various portions of widgets can be a mess(gtk2 with Pango markup lets you mix colors and fonts in a single label), no drag-and-drop support( yes, Gtk2 will let you drag files from one widget, and dump them onto another), better threads support, etc, etc, etc.

Now I'm not trying to disparage Tk. It is very good for what it is, but Gtk2 has alot more thought being put into it. So which would you choose for a big, long-term project?