In Europe and North America, industrial activity has led to special recognition of sites with mega-contamination (mega-sites), distinguished by the magnitude and chemical complexity of their contamination. They can become nearly intractable problems due to complex and intertwined influences of socio-economic, hydrogeological, biological and political elements. Mega-sites are, and will continue to be, part of the inherited environment in 21st century societies and their long-term management presents new challenges that we specifically address in this paper. We use lessons from the mega-site case study of Leuna, Germany, to develop new long-term strategies for situations where conventional remediation and management approaches may be untenable. These lessons highlight the risks associated with incomplete consideration of complex socio-ecological interactions that cannot easily be analysed or their influences predicted. Accordingly, we propose a broader risk management approach entailing iterative, adaptive assessments of both site based risks and environmental sustainability criteria. We then re-examine project planning approaches for potential mega-sites, proposing that they be expanded to include stakeholder involvement in the design of anticipative post-closure coping strategies. The underlying modelling challenge is to identify sufficient relevant problem factors to cover the broad scope of site characteristics without becoming ensnared in irresolvable detail.