Thank you, waedi!
That did allow signal to flow out into my outboard gear!

One last question, now it sounds like PH 3/4 (where my headphones are plugged in), are trying to monitor both the outgoing signal and the incoming signal (like a feedback loop).

Do you know what settings or where in the manual to adjust to fix this?

Thank you again!

I changed the source to USB 1/2 from Auto and am still experiencing this.  I use Studio One with Pipeline XT.

Any more ideas, or better method for setting this up?  I’m open to changing outputs, etc. if it will allow this to function with the outboard gear

Thank you, waedi!!

Confirming that monitoring is turned off.

The most important thing for me is to hear the processed signal coming from the outboard gear. 

But, ideally the processed signal from the outboard gear.  As well as any unprocessed tracks (excluding the one routes to outboard) that are within the project, for mix context. 

For example, if the guitar is being routed to outboard gear, then I want to hear the guitar signal coming from the outboard gear.  But, also hear the unprocessed drums and bass within the studio project.

Check one signal at a time, until you figured out the routing.

Yes, if you switch the unit to 'Multichannel mode', see pages 42 & 43 here:
https://www.rme-audio.de/downloads/adi24pro_e.pdf

You will also need to set the 'Rear TRS Source' to Phones 3/4, that is in the I/O menu > Phones Out 3/4 > Settings

This is all Studio One routing-related.
ADI-2 itself can’t produce a feedback loop, e.g.

I’d suggest to go through it again, one step after the other.

• First, and most important, select and set a fitting “Mode” inside ADI-2.
USB- / Class Compliant Multi-channel mode gives separated access to all inputs and outputs, so I suggest to use it, see manual page 42, 43.

The block diagram page 43 is valuable to understand the routing inside ADI-2.

Unplug USB, then set:
SETUP / Options / Device Mode/ DSD / Basic Mode: USB
SETUP / Options / Device Mode/ DSD / CC-Mode: Multichannel
Replug USB.

• Next, decide if you want to use the Rear TRS outputs with Channel 1/2 or 3/4.
Depends on your analog connections.
Set: I/O / Phones Out 3/4 / Rear TRS Source: Line1/2 (=default) or PH 3/4.

• Everything else is Studio One routing.
Configure the Studio One’s Ins and Outs.
Then check one signal path after the other, starting with the main monitoring.
For the analog processing chain, make a direct cable connection first, ADI-2 out to in, bypassing all analog stuff to be sure this path works.

Yes of course, one path is for monitoring, the other for the analog FX loop.

So first you have to decide if you want to do your monitoring through 1/2 or 3/4.
Basically 1/2 is intended for moitoring, specially if you often switch between speakers and headphones.

Refer to the block diagram on manual page 43: there’s an input selector for 3/4 available.
Set the source for PH3/4 to USB (3/4):

I/O / Phones Out 3/4 Settings / Source: USB

Unplug headphones from 1/2.
There’s a function/option that can mute back Line Outs when headphones are plugged, I’m not sure how the setting defaults:
Or set:
SETUP / Options / Phones / Toggle Ph/Line: OFF
SETUP / Options / Phones / Mute v. Ph. 1/2: OFF
SETUP / Options / Phones / Mute v. Ph. 3/4: OFF

I still cannot agree with MC about the logic of this functionality, for the moment switch all off.

Later you might use:
SETUP / Options / Phones / Mute v. Ph. 1/2: ON