The goal of this Thesis is to propose novel methodologies to address crucial issues of indoor positioning systems (IPS). The problems addressed in this work are met throughout the whole life cycle of an IPS conception, realisation and operation, from designing innovative positioning methodologies to defining evaluation and tuning methodologies. Therefore, this Thesis initially investigates and reports the user needs and requirements concerning the wayfinding problems at an important use case: Geneva's University Hospitals (HUG). Following, it proposes innovative solutions that construct a robust IPS, along with ways of seamlessly switching from indoor to outdoor positioning. To strengthen the robustness of the system and reduce the required calibration effort, algorithms of automatic recalibration of the system are proposed and analyzed, addressing the problems of device and environment diversity. Lastly, well-defined methodologies of evaluating, comparing and optimally tuning positioning systems are proposed, addressing the most trending issues of the IPS community.