I'm running a SAMD21 XPRO board that uses the EDBG USB port for programming and debugging and the Native USB port for Serial I/O.
What I've not figured out how to do is to run the debugger (EDBG) and view the Serial Monitor at the same time. It appears that the Serial Monitor is tied to the EDBG. Is there a way to switch the Serial Monitor to the Native USB port?
It is also possible to open a new Arduino IDE 2.x window, select the Native USB port in the Tools > Port menu, and then use the IDE's integrated Serial Monitor (Tools > Serial Monitor) for this purpose. Unlike the classic Arduino IDE, where all windows of the IDE instance shared the same board and port selection, Arduino IDE 2.x allows independent board and port selections in each window.
In this particular case, there isn't really a lot of benefit to that approach other than that everyone who has the Arduino IDE installed already has the Serial Monitor available. So I think the advice provided by markd833 is good.