To build a real-time chat application with Django and Twilio Programmable Chat, developers need to consider several concerns such as user modeling, channels, access levels, and message display. The process involves setting up a virtual environment, installing dependencies, creating a new Django project, and configuring the Twilio Chat service. Developers can then create views to fetch data from the database and templates to render the chat interface. To enable live chat functionality, developers need to add endpoints for token generation, channel creation or joining, message sending, and pagination. The app also needs to be tested with sanity checks to ensure that it functions correctly. With this guide, developers can build a basic chat application using Twilio Programmable Chat and Django, and explore more capabilities of the API.