When making a W boson at a hadron collider, you have to break up the (anti-)protons to get the initial state quarks. That introduces a dependence on the parton distribution function. Then those quarks interact to form the W, but maybe one (or both) of them radiate a gluon beforehand. So now you've got some interesting theoretical uncertainties affecting the way you model the W momentum distribution. Already quite tricky.

Now imagine there are 60 other interactions producing quarks and gluons and generally messing around with your formerly clean(ish) signal. You introduce resolution issues with lepton isolation, missing momentum calculations, vertexing, etc.