This series targets 'tween girls and showcases bright, curious girls putting science and engineering to work. Each episode follows a different group of middle school girls as they answer real-life questions and make unexpected discoveries. Recurring animated characters, Izzie and Jake, embark on their own adventures and call on the SciGirls for help. The show integrates a companion website into the TV series, where at the beginning of each show, television viewers follow Izzie onto the website, as she picks a group of SciGirls to help her. Izzie launches the video and follows the SciGirls' live-action story, learning as she goes.