One site with many regions or multisite

I’m not quite sure what you mean by “regions”?

You can ignore regions if you find it confusing but I think the text in the body of the message is straight forward.

Rather than creating 50 different domains and instances of WP, I thought it would easier to have an office’s home page as https://www.mydomain.com/myoffice1 or https://www.mydomain.com/region1..region100 is that appeal to you more.

The problem I run into is the management. How does one give access to only the pages that are associated with their respective region or city.

Thanks.

Note that the the WP sites are loosely connected to the “main” site. This is more of a problem for WP subdomain. This includes the user base which is shared among all sites.

After creating a site, you add users with roles to that site. That is how users get (privileged) access to a site. By default the user will have the lowest level privilege (subscriber) to the other sites. If you do not like that behavior you could use plugins to change it

If you go the multisite route with domains you would need 50 domains but not 50 instances of WP – that’s the whole idea of multisite – you have one instance of WP that in effect can act like x number of instances.

You would need to map each of your domains into each new site using the MU domain mapping plugin, which can be a bit fiddly setting up. But then you have 50 sites, which can all share the same plugins and themes but have different users and/or shared users and different content in each.

Alternately you use one site and use plugins, as jkhongusc says, to set user privileges for who can access what.