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A systems methodology to examine large scale interrelated complex global systems governing natural resource use, population, economy and global health is developed. Evaluates the individual disciplines and their integration as a system. Integrated assessment (IA) examines if the looming peak in world oil production, and the post-peak oil era can intensify the HIV/AIDS epidemic. Questions include:§When could the world reach peak oil?§How will the growth of middle class India and China affect oil use?§What are the economic implications for HIV/AIDS funding in a post-peak oil era?§What is the humanitarian cost in lives lost per barrel of oil deficit?§A range of models are developed and integrated in a decision support future assessment system used as a reasoning guide. An interactive cybernetic approach incorporating the global earth/human dimensions is applied to manage the many aspects of complexity and uncertainty. IA is enhanced by a decision-making paradigm that utilizes real data, a family of multi-level hierarchical models, and a human-in-the-loop approach. Corner scenarios envelope the scope of future development and potential scenarios demonstrate possible futures therein.