As Tony says, you can use the internal drivers for extruders and external drivers for axes. See https://duet3d.dozuki.com/Wiki/Gcode?revisionid=HEAD#Section_M584_Set_drive_mapping.
If you do go the Duet+DueX2 route, you may need to level-shift the signals for the external drivers to 5V. One possibility would be to connect both a DueX2 and the external stepper driver breakout board to the Duet, using a 50-way ribbon cable with 3 connectors on it. I don't think this has been done before, but I can't see any reason why it wouldn't work. On the external driver breakout board you would avoid using the 2 motor hannels that are used by the DueX2.
HTH David