To become an Appium Desktop Ninja, you need to gain foundational knowledge of the open-source test automation framework, which allows teams to automate mobile applications on various platforms. With Appium Desktop, a graphical UI application for Windows, Mac, and Linux, you can execute automated tests on native and hybrid devices, inspect web elements, and more. The six-part Tech Talk series, led by Wim Selles, provides the necessary knowledge to get started with Appium Desktop, covering topics such as theory and background, configuration options, usage of the desktop application, managing different versions, integration with Sauce Labs, and hidden features. By following this series, you can successfully accomplish your mobile automation initiatives and become proficient in using Appium Desktop.