We are currently using on-prem Exchange and xeams accurately identifies the users' associated email addresses (or aliases).  We are going to move to Office 365.  Will xeams still be able to identify the associated email addresses once their mailbox is hosting at O365?

I assume xeams is associating the email addresses via Active Directory integration.  We will still have AD on-prem...will we need to point xeams AD integration to O365 or will it still get what it needs from the on-prem AD?

Since you're planning to leave AD on-prem, configure Xeams to use that AD. I assume you will be syncing the on-prem AD with O365. In that case, everything should work fine.