Do I have to regen tool path in the middle of a tool change if I rezero Z. 

Order of operations... 

1.  Set Mach to stop spindle and wait for start on a tool change. 
2.  Manually change tool and reset zero Z.

3.  Regen Toolpath???

4.  Press start. 

Yes, I know I have to regen toolpath when I change X or Y Zero. 

The reason I ask is it can take some time on complex 3D jobs to regen the toolpath. 

The answer is no.  You don't.  For anybody else that wanted to know.  As soon as I manually set a new value for Z it skips to the next instruction and waits for me to press start.