From the documentation for SendMail:

On desktop systems, SendMail requires certain user mail settings. These can be defined through Preferences > Internet & Mail > Mail Settings in the notebook front end or by using SetOptions[SendMail,MailSettings]. SendMail will attempt to send email via the Wolfram Cloud if these settings have not been provided.

Hi Kevin,

Using SendMail through my Gmail account works fine with 2FA. Check the settings in Mathematica. Use your Gmail address in the Username and From Address boxes.

Then set up an "app password" as described here. For "App" choose "Other" and enter whatever name you want. I used Wolfram. Copy the password generated and save it in your password manager or other secure location. To test

SendMail["wlmailtest@wolfram.com", "Here is the body of the message."]

A dialog box will pop up, enter the app password generated above.

If that does not work, please share the code you evaluated and the error message displayed.