Audio interface does not connect when Mini M4 already on, only with boot up or unplug/replug every time. Any help would be appreciated.

Commiserations! Thank you kindly for your reply, and for sharing your experience. Thank you too, for taking the time to try contacting the experts first.

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Re: "I'm wondering if I can do anything about turning my interface on & off at my discretion & have it connect to the Mini without having to do the above mentioned, like it used too & should."

Wondering which apps you use the audio interface with:

Eg: About third-party Audio Units and external device compatibility in Logic Pro and Final Cut Pro on Mac computers with Apple silicon - Apple Support may have tips,

and

Whether there may be interference from unnecessary third-party apps like virus-checkers, ad-blockers, cleaners and the like (even VPN if not provided by an employer). If installed, you can try turning the apps off, although they may be still running in the background. Better yet is to use uninstallers from their developers.

Also: any third-party apps you find necessary need to be kept up-to-date so they do not cause compatibility issues.

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Another possibility: There might be interference with other wireless devices.

For tips, see: Resolve Wi-Fi and Bluetooth issues caused by wireless interference - Apple Support

Re: "Audio interface does not connect when Mini M4 already on, only with boot up or unplug/replug every time."

... After a new Mac Mini M4 Pro purchase ..,

With a new system I would have thought it would make sense to simply turn on & the handshake would occur but alas... my current issue..."

Wondering how recently your purchase was made:

ie: You may or may not be eligible for complimentary support from Apple's experts.

To check: See details + Choose your country or region - Official Apple Support

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If eligible:

One stop for technical support, Apple hardware service, and software support.

Call Apple Support at 1-800-APLCARE (or use the Support app)

or visit the AppleCare Products page for more information.

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If not eligible:

Please let us know if you need more help from the community with this issue.

Thank you kindly for your replies, and for sharing more about what you have tried.

Wondering whether it may be worthwhile to contact the support team at Focusrite ... they may (or may not) have helped deal with a similar situation before.