Despite their enormous potential the use of Indoor Localization Systems (ILS) remains seldom. One reason is the lack of market transparency and stakeholders’ trust in the systems’ performance as a consequence of insufficient use of Test and Evaluation (T&E) methodologies. The heterogeneous nature of ILS, their influences, and their applications pose various challenges for the design of a methodology that provides meaningful results. Methodologies for building-wide testing exist, but their use is mostly limited to associated indoor localization competitions. In this work, the T&E 4iLoc Framework is proposed - a methodology for T&E of indoor localization systems in semi-controlled environments based on a system-level and black-box approach. In contrast to building-wide testing, T&E in semi-controlled environments, such as test halls is characterized by lower costs, higher reproducibility, and better comparability of the results. The limitation of low transferability to real world applications is addressed by an application-driven design approach. The empirical validation of the T&E 4iLoc Framework, based on the examination of a contour-based Light Detection and Ranging ILS, an Ultra Wideband ILS, and a camera-based ILS for the application of Automated Guided Vehicles in warehouse operation, demonstrates the benefits of T&E with the T&E 4iLoc Framework.