When I try to change a nested MCs property from the main timeline, I get no
response. I can run the same code inside the MC and I have no problem. Is it
possible to target a nested clip to change its properties?

That is absolutely possible. It is hard to say from your description where the
bug exactly lies. Can you give us more details...

Did you target the clip correctly? _root.instanceNameOfTheClip.parameter =
"something";

Yep, if I try:

_root.motherClip.targetClip._visible = false; // nothing

inside the targetClip:

onClipEvent(load) {
_visible = false; //works
}

tried it all kinds of ways too.

so your motherclip sits on the stage and when you open the motherclip there
sits the targetClip, right? And both of those have been named in the
properties window in the instanceName field as motherClip and targetClip.

Does either the motherClip or the targetClip contain any sort of animation or
is it all one frame?