I know that you can add a vault to a Mylio install that is in an external drive but this is only allowed for secondary vaults. The primary Mylio install still needs its own photo repository on internal storage.
This is just not practical in some situations.
I used to have an iMac with a 2TB fusion HDD that I had on all the time. This had a vault on it, along with an SSD vault that was attached and a vault on a NAS.
I sold the iMac as I went to a laptop. I then found I had no central Mylio to host vaults, as at this point we are all iOS or MacBooks. To work around this I tried running Mylio in a Win10 VM on my Synology but my 2015 NAS is not strong enough. Temporarily, I repurposed a 16 year old PC I had collecting dust, installed Win10 and a couple of 3TB drives got it work in RAID1 and that is my central Mylio hub for now as my primary vault with the NAS as a secondary. BUT it is slow! To sync ~8,000 photos recently took around 12 hours.
I would like to junk that ancient PC and replace it with a Mac Mini with 10G ethernet to act as server duties, including Mylio. That is $700 but only has 256GB of memory. I need at least 1TB for Mylio which would necessitate the 2TB version of the Mini but that costs $800 more; not worth it. I would rather plug a 2TB external SSD I already have into it and use that as the primary vault location but this is not permitted at the moment.
Currently the only option I see is to install Mylio with thumbnails only, keep documents/video smaller than: none, and set up vaults on external SSD and NAS. Not sure if that would work. Last time I tried something like this, it did not work properly as Mylio wants to pull from the internal repo and will not pull originals from the vault. To get originals you then have to manually sync the original to the internal storage which totally negates the intent of not using the internal storage for this.