Systemic risks are potentially harmful events, that could severely disrupt an entire industry or economy. Examples include the bankruptcy of keystone companies and biosecurity incursions. According to the United Nations, detecting and managing systemic risk represents one of the main challenges of the 21st century. Due to increasing complexity and interconnectedness of today’s social-technological-biophysical systems, stakeholders relying on individual disciplines to systemic risk detection, or a combination of disciplines that are not well coordinated, will fail to promptly identify key early warning signals of threats. Our paper argues that transdisciplinary approaches are required to make comprehensive and integrative assessments of complex systems. To support stakeholders undertaking such assessments, we propose a framework that will assist them in: (1) better understanding their system and the risks to which it is exposed; (2) selecting complementary disciplines, theories and methods that are relevant to the system and risks in question; and (3) integrating knowledge from these different disciplines to detect a wide range of early warning signals of systemic risk. The framework can be used as a foundation to build transdisciplinary approaches to risk detection.