There is already a lot of information about how to control your hotkeys in a XenApp session.
At a customer, this still led to some confusion about when and where the config should be done.
This was kind of tricky because they saw that external users experienced different behavior than internal users.
So the first stop was, which interface is used by which user. Internally the users were directed to the internal Citrix Web Interface (yes, old school).
So on the old Web Interface the Default.ica in C:\inetpub\wwwroot\$$websitename$$\conf\ is used to edit the available hotkeys. For a full explanation about this, check https://support.citrix.com/article/CTX140219
The external users are directed to a Netscaler also using the Web interface but this time the one that is available in the Netscaler. So editing the hotkeys must be done in the Netscaler. Read more