AnywhereUSB Plus Manager shows red cross and can't connect after initial configuration

Check the network settings: Are you able to ping or HTTP to the AnywhereUSB Plus hub?

Follow the setup / get started instructions:
https://www.digi.com/resources/documentation/digidocs/90002383/default.htm#device/anywhereusbplus/content/tasks/t_initial_connection.htm

most often you forget to "APPLY" the admin password in the web GUI:
https://www.digi.com/resources/documentation/digidocs/90002383/default.htm#device/anywhereusbplus/content/tasks/t_change_default_pw_hub.htm

please on the Web interface go to System > Device Configuration > Authentication > Users > admin > Enable and enter a password (you may enter the one printed on the box or a new one) and "APPLY" on the upper right button.

Without above step, you might do further settings, but you will still get the red cross "unable to connect".

Follow all steps here:
https://www.digi.com/resources/documentation/digidocs/90002383/default.htm#device/anywhereusbplus/content/container/cont_getting_started.htm