Background of the Study The aims of this study was to specifically investigate the differences in culture, attitude towards life and social networks between Australian and Taiwanese men and women in addition to determining the factors that predict midlife men and women's quality of life in both countries. Because individualism and collectivism are the two most thoroughly researched constructs in inter-cultural and cross-cultural studies we should look at how these construct affects societies. The theme for individualist cultures (such as Western cultures) is autonomy, while the theme for collectivist cultures (such as Asian cultures) is connection. Most literature available on individualism and collectivism note all cultures have different values that influence their society and ultimately a person's individual health outcome. Very little work has been undertaken in this domain in Australia or Taiwan, particularly in the area of midlife transition and from a cultural perspective. Methodology Data was collected from a cross-sectional, supervised self-administered survey using census data and a probability proportional sampling (PPS) strategy on a general population of men and women aged 40-59 years old who live permanently in Brisbane, Australia and Taipei, Taiwan. The study population was divided into 163 Statistical Local Areas (SLAs) in Brisbane, and 449 Local Government Communities (LGCs) in Taipei. Sixty clusters were randomly selected using probability proportional sampling (PPS) to obtain 30 Australian clusters and 30 Taiwanese clusters. In this study, the 30 (areas) by 7(people) method was used with an additional strategy. The variables were measured including: culture (vertical and horizontal individualism and collectivism), attitude towards life (the total score of optimism), social networks (the total score of emotional, informational, affectionate, tangible, and positive social interaction) and quality of life (physical, psychological, social, and environmental health), social demographical factors and religion and spiritualty. The data analysis procedure included descriptive, bivarite and multivariate multiple regressions and classifications and regression trees (CART). A comparison of the linear regression and regression tree results were discussed. All data analysis was performed by SPSS and S-Plus softwares. Results The overall response rate for the study was 84.2% for midlife Australian men and women and 88.4% for midlife Taiwanese men and women this resulted in 278 Australians (45.3% men) and 398 Taiwanese (35.4% men) providing data to be analysed. Findings in this study indicated country of residence has an overwhelming impact on quality of life with significant differences seen between midlife Australian and Taiwanese men and women (F4, 666= 59.31, P< .001). Results suggest midlife Australian men and women have a better quality of life than midlife Taiwanese men and women. In addition, a comparison of the linear regression and regression tree results reveals that two models identified the same major affect variable for different countries of residence: which was attitude towards life in midlife Australians and social networks in midlife Taiwanese. However, regression trees were able to capture important nonlinear effects as well as interactions between cultural attribute variables. This study demonstrated culture significantly involves multiple functions and interacts with attitude towards life, social networks and individual factors to influence a person's quality of life. The interaction of cultural circumstances and the internal and external factors involved, show less comparative attributes and increased equality attributes, defining the need for people to have a good social networks and a healthy positive disposition. Conclusion Because of the ever increasing flexibility of world travel and a global population, people have much more opportunity to interact with many other cultures which would create improvement in learning opportunities and better health management effectiveness for people the world over. This study has addressed and contributed to the assessment of multi-cultural quality of life research and has important implications for all health professions in addition to government departments and organisational policy makers of both countries. And finally, this study has identified that there needs to be a concerted effort to implement major policy shifts in the near future because of the changing fabric of modern societies. At the same time technology and globalisation have advanced rapidly and point to new opportunities within and across countries for more diverse approaches in research and the implementation of policy initiatives to occur. This study has highlighted that opportunities exist to reflect on current policies for Australian and Taiwanese societies to provide enhanced opportunities to care for the growing midlife populations.