When I try to use shift for a modifier, the icon will change but the ability won't cast. I have done lots of troubleshooting and the macro works fine when not using Mega Macro. I have checked all keybinds to ensure that shift is not being used in combination with my spell keybind.

Hello. I'm having the same issues here, and covered the same test cases you done.

Figured it out. Shift is not picked up by the addon cause you have SHIFT as a modifier for Locked Actionbars.
I set the modifier to none, and it worked instantly.

Not sure how to have it detect it separately. But if people are having problems with shift. This is the reason.