According to this post in the Salesforce community, it is possible, but very complicated and advanced. Overriding user profile page with a visualforce page - Salesforce Stack Exchange A simpler work around maybe to add a navigation button to your Skuid page for “view/edit users”. It could bring up a Skuid page that has a table of users and allows you to choose a user to edit that would bring up a field editor as a pop up of drawer. This doesn’t override the the reference links to users, so if someone clicks their name, it will still take them to the standard Salesforce user detail page. You could address this by removing user reference fields from your read mode skuid components and replacing them with template fields that display the user name as hyperlinks to your Skuid user detail page. You can also replace the Salesforce header completely with a custom Skuid header so that the menu options can be controlled to redirect to your Skuid page instead of the Salesforce user page.