This paper looks at a very topical challenge: how to appraise the sustainability of a city, a region, a policy, or programme. As the theme of sustainability is intrinsically multidisciplinary and multisectoral, this suggests that effective appraisals should likewise be based on a holistic or integrated assessment (IA) approach. This paper outlines a conceptual framework and a practical tool for such an approach. We first review the concepts of sustainability for an urban–regional unit, drawing on an investigation of integrated planning for long-term sustainable development in a case study of Greater Manchester, UK. From this we develop a IA framework which helps to map linkages between environmental, economic and social factors. One practical application is the Integrated Sustainable Cities Assessment Method (ISCAM), a scenario accounting system for the total environmental metabolism of a city or region. These scenario accounts are also useful for strategic assessment and sustainability appraisal of policies and programmes, where indeterminate and cumulative effects can be placed in a whole-system context of trends, projections, goals and targets.