This chapter provides an insight into the role of systems science for sustainability assessment. In the first part, we present seven axioms that have been derived from system-theoretical perspectives and show their relevance for sustainability assessment. Following these axioms, we propose a way to structure and analyse systems following four system characteristics: (1) system boundary and interactions with the external environment; (2) purpose, goals, and associated decision-making drivers and criteria for the system; (3) system structure (subsystems, elements, and their interactions), dynamics, and emerging behaviour; and (4) system information, outcomes monitoring, and learning. These four characteristics were applied to study, first, the historical development of the energy system analysis and, second, an Australian urban systems-transformation initiative. The systems-analysis framework presented provides a good basis for putting the elements of a system analysis into their broader context, and designing purposeful interventions. Especially for more transformational change, the alignment of stakeholder values, institutional arrangements, and available knowledge become key leverage points.