Digital Twins are being used more and more frequently and provide information from the Real Twin for different applications. Measurements on the Real Twin are required to obtain information, which in many cases requires the installation of supplementary sensors. For their conception and design, it is particularly important that the measuring principles are selected purposefully and the appropriate sensors are integrated at the goal-oriented measuring positions without impairing the functions and other properties of the Real Twin by the integration of these sensors. In this article, a “Design for Digital Twin” approach is discussed for the systematic procedure and demonstrated using a multi-staged gearbox as a concrete example. The approach focuses on the mechanical and hardware side of the Real Twin. For the systematic conception and design of the Digital Twin solution, an understanding of the stakeholder demands and the expected use cases is necessary. Based on the stakeholder demands and use cases, the relevant product properties can be determined. Using the relevant properties, an iterative process of conception, design, and analysis takes place. The conception is carried out by means of target-oriented cause–effect analyses, taking into account systemic interrelations of the Real Twin components and systematics for the selection of measurement principles. Systemic considerations, combined with an effect graph, allow for the analysis and evaluation of disturbing factors.