Outlook 2013, multiple email accounts and encrypted email: Only last S/MIME settings used

The short answer I believe is no. This is setting is a profile setting, so all mail accounts on the same profile will inherit it. You could setup different profiles for each account, but that will require you close and restart outlook to access those accounts.

Two other methods that may work:

1. VBA/Macros - Use these to create messages withs specific settings applied
2. Outlook custom message templates. I did look at the available fields but didn't notice any for SMIME. I don't really use custom template so may have overlooked it or it may need to be implemented or access in some other way.

A personal certificate (such as you might get from Comodo, and which has an associated private key) lets you sign a message as Definitely From You, though the recipient will need to see and trust the certificate to verify the authenticity of the signature. Outlook (by default) automatically sends the certificate with any signed message, though it also probably is not signing the messages by default (you have to change a setting, or toggle signing on each message).

If you want to ensure that the email message isn't going to anybody other than the recipient, you need to have a certificate for the recipient, and you use that to encrypt the message to the recipient. You can only encrypt to people whose certificates you have. You can install people's certificates the same way you install any other certificate in Windows - double-click the file and select Import - or Outlook will do it automatically if they send you a signed message and you try to reply.

Together, signing and encrypting a message provides good security; you know where the message came from (and that it wasn't tampered with in transit), and you know where it went to (or at least, you know that nobody else was able to decrypt it).

In order to set up email encryption and signing (and change the default settings) in Outlook, you go to File -> Options -> Trust Center -> Trust Center Settings -> E-mail Security.

With that said, while I've attempted to answer the question you actually asked, you might be having a different problem. I'd guess that the problem is that you normally use Outlook with co-workers, and send them emails that your Exchange server can verify are correct and trusted. When you send email to any external address - such as a Gmail address, but I would expect it to happen with other external addresses too - Outlook can't verify who the recipient is, and is warning you that you might be sending to somebody you don't mean to (or just that you are sending to outside the company in general).