Handling vendor prefixes inSASS can be managed by using mixins or tools like `autoprefixer`. Define mixins for common properties with prefixes, such as`@mixin flex() { display: -webkit-box; display: -moz-box; display: -ms-flexbox; display: -webkit-flex; display: flex; }`. Alternatively, use `autoprefixer`in your build process to automatically add necessary prefixes, ensuring cross-browser compatibility with less manual effort.