Misha Mansoor recently made a quick little video showing how Overdrive pedals are generally used with Modern/High Gain amps and how he personally likes to set his signature Pro Tone Bulb Deluxe Overdrive with my amps and Axefx.
For this demo I am using my Mesa/Boogie Dual Rectifier (Early 90’s Rev F).
That is plugged directly into a Two Notes Torpedo Live which is both a Loadbox for the amp and a cab sim (on which I loaded a tone match of my Zilla 2×12 cab).
This is going out to my Fractal Axefx II (Mainly so I would have a tuner handy and using a slight noise gate to cut power amp noise) and out to a Focusrite Liquid Saffire 56 Interface.
The guitar being used is a Jackson Custom Shop 6 string loaded with Bare Knuckle Pickups Juggernaut set.
The guitar track has no processing on it so that you can hear what the raw amp signal sounds like with and without the pedal.
Hope this is helpful!