Answer
Two things typically need addressing together. First, enable ClickOnce support in the browser itself — in Edge, go to edge://flags, search for 'ClickOnce,' and set ClickOnce Support to Enabled, then restart the browser. Second, if the .vsto link still doesn't work after that, check for a conflicting 'IFS EE Link Handler' browser extension/handler — disabling it has resolved cases where it was intercepting or interfering with the .vsto ClickOnce link even with ClickOnce support otherwise correctly enabled in the browser.