Mail Merge is a technique that utilizes a template to send personalized emails to multiple recipients efficiently, especially beneficial for high-volume sends. The process involves using Python and the Nylas Email API to automate and customize email content by replacing placeholders with recipient-specific data stored in a .csv file. The guide outlines setting up a Flask web application to manage this process, including creating and configuring a Python environment, installing necessary packages, and developing the application structure with templates for dynamic subject and body content. The application ensures all required fields are filled before sending emails and uses the Nylas API to draft and dispatch personalized messages to recipients. The mail merge operation is demonstrated via a user-friendly interface, allowing users to upload a .csv file, specify email content, and view the results, all accessible through a local host web server.