Many challenges that confront today’s society are complex and dynamic and require new perspectives to arrive at solutions that could not be found before. Finding such new perspectives is part of a process called reframing and one of its key stages is theme investigation. Understanding a problem thoroughly is crucial for creating effective solutions and theme investigation offers insight into human and social themes that underlie complex challenges. This article discusses how to investigate such themes, to deepen our understanding, to find a starting point for reframing and creating innovative solutions. This work explicitly experiments with variation (conceptual, personal, and methodological) as a guiding principle for investigating human themes in real life cases. A process, best practices, instruments and tools for theme investigation are presented and discussed.