You can set up SMTP Restrictions by logging into WHM, searching for "SMTP" (1), selecting SMTP Restrictions under Security Center (2), and reviewing SMTP Restrictions (3).
Inside the interface, click the Enable button to start the service.
SMTP Restrictions is a feature in WHM that stops users from bypassing the mail server to send mail. This service is useful because bypassing mail servers is a common practice of spammers. You'll only receive mail from root connections, Mailman mailing list software, and mail transport agent (MTA) to remote SMTP servers by setting up restrictions.
Selecting Tweak Settings will take you into WHM >> Tweak Settings, where you can also adjust SMTP settings like:
Restrict outgoing SMTP to root, Exim, and mailman
Allow users to relay mail if they use an IP address through which someone has validated an IMAP or POP3 login within the last hour (Pop-before-SMTP)
Add X-PopBeforeSMTP header for mail sent via POP-before-SMTP