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This chapter shows how to construct and test case-based macro models. The chapter makes use of national data to examine influences on quality-of-life of national cultures as complex wholes and entrepreneurship activities in Brazil, Russia, India, China, Germany, and the United States (the six focal nations) plus Denmark (a small-size, economically developed, nation). The study tests McClelland’s (1961) and more recent scholars’ proposition that some cultural configurations nurture entrepreneur startups, while other cultures are biased toward thwarting startups. The study applies complexity theory to develop and empirically test a general theory of cultures’, entrepreneurship’s, and innovation’s impact on quality-of-life across nations. Because culture represents a complex whole of attitudes, beliefs, values, and behavior, the study applies a set-theoretic approach to theory development and testing of alternative cultural configurations. Each of 28 economical developed and developing nations is scored for the level of the national cultures for each of six focal countries. The study selected for the study enables multi-way comparisons of culture-entrepreneurship-innovation-QOL among large- and small-sized developing and developed nations. The findings graphically present the complex national cultural configuration (x-axis) with entrepreneur nurture/thwart (y-axis) of the 28 nations compared to the six focal nations. The findings also include recognizing national cultures (e.g., Switzerland, the United States) nurturing entrepreneurial behavior versus other national cultures (e.g., Brazil and India) thwarting entrepreneurial behavior. The study concludes with a call to recognize the implicit shift in culturally implicit thinking and behavior necessary for advancing national platforms designed to successfully nurture entrepreneurship. Entrepreneur strategy implications include the observation that actions nurturing firm start-ups by nations low in entrepreneurship will unlikely to be successful without reducing such nations’ high levels of corruption.