Leaving target processor paused nios ii multiprocessor application
Basically, there are a couple of issues that could be a problem:


The CPU is being held in reset due to some other peripheral not correctly starting up.
There is a software error launching the debugger software. I don't think it's this because you mention this software has worked before.


It's most likely that it's #1 - one of your CPUs is being held in reset (or both) due to (for example,) the PLL not locking or something else is not coming up correctly.

It's probably best to check what the CPUs are dependant on to come out of reset and ensure that those are all starting up correctly.

Since you mention that this works for single processor designs, double check that your CPU resets are all connected correctly according to this multi-processor tutorial,   see table 1-3 and onwards, from page 1-23.