SASS (Syntactically Awesome Style Sheets) is a CSS preprocessor that allows for variables, nested rules, mixins, and more. It can help with issues like large CSS files by breaking them into smaller partials and using inheritance. Popular Drupal themes like Omega use SASS and an architecture with base and sub-themes. Creating a new Drupal theme involves key files like .info and .tpl.php template files. The Drush command line tool can help generate a sub-theme skeleton.