Users receive HTTP response 404, due to traffic landing on wrong servers on the back end.
Content Switching and Load Balancing configuration on the NetScaler is correct.
To resolve this issue enable Drop Invalid HTTP Headers feature on NetScaler:
Note: Ensure that you always select this option. It helps in detecting the invalid HTTP headers.
Expand the System node of the Navigation pane on the appliance.
Select the Settings node.
Click the Change HTTP parameters link on the Settings page.
Select the Version 1 option.
Note: Select the Version 0 option only if the environment has earlier releases of web browser that do not support Cookie Version 1.
Select the Drop invalid HTTP requests option.
When the Content Switching virtual server receives an HTTP invalid/corrupt header next packets from same source IP may be redirected to a incorrect destination Load Balancer.
You can refer to this counter (increases) to confirm the issue - http_err_noreuse_InvalidHeader.