Start with the requirement
Choose based on sender identity, recipient scope, client capability, network constraints, volume, and who will operate the solution.
Choose smtpify365 when
The client can authenticate over STARTTLS, should send as a licensed mailbox, and cannot implement OAuth itself. It does not require the client site to expose a static public IP to Microsoft.
Choose Microsoft 365 SMTP relay when
Your administrators can configure and maintain an Exchange Online connector, certificate or static IP authentication fits the network, or the sender address does not need a mailbox.
Operational difference
smtpify365 creates credentials per connection. Microsoft relay centralizes control in Exchange Online connectors and network identity. Neither choice should be selected without reviewing current Microsoft guidance and organizational requirements.