Create a virtualenv, activate it, and then pip install -r requirements.txt. (Make sure it's a Python3 environment; some of our dependencies require it.)
Create an account with MongoDB's cloud service; it's free for a very small cluster. Set up an admin user with a separate password, create an IP whitelist and connect to the database cluster to make sure it's working. (Install mongodb to your machine, with Homebrew, for example.)
Docs:
Update config.py with your MongoDB credentials/URIs (be sure to get the full URI connection string from the "Connect Your Application" dialog), your email address in the ADMINS list and some dummy mail server credentials.
Create a .env file (or otherwise configure environment variables) for your MongoDB password, API key, and other sensitive variables, based on .env.example. server_name must be set to the host/port at which you'll be accessing the server; for example, for local testing you might set it to smilodon.localhost:5000 and add 127.0.0.1 smilodon.localhost to your hosts file. server_uri should be the full address and protocol that it will be found at, e.g. https://smilodon.social.
For local development, you may wish to disable SSLify (in app/__init__.py), to access the server over HTTP rather than HTTPS.
Install Heroku (brew install heroku). (You could also use Foreman or Honcho.)
heroku local should run the server on your local machine. You can access the server at the server name you configured above, for example, http://smilodon.localhost:5000.