Information system (IS) success is still one of the most researched topics in the IS discipline, but most research on defining and measuring IS success was conducted in North America. As the world globalizes, multinational organizations consider information technology and IS as crucial and necessary tools to glue together all of their units. Moreover, IS standardization (i.e., the same IS implemented in all the units), particularly through enterprise systems (ERPs), has attracted these organizations because of the economic benefits standard applications can eventually yield to. However, researchers in the international management discipline have assessed that culture may be a major factor that influences organizational structure and management practices. Some researchers in the field of IS have also confirmed that national cultures do, indeed, have an impact on IS design and acceptance. As culture is defined as “a shared system of meaning,” the success of IS should hold different meanings in different cultures. We found only sparse research work on how people from different national cultures perceive, define and operationalize IS success. The objective of this chapter is twofold: first, discuss why organizations that intend to standardize IS in different cultures should consider culture as an important factor in the achievement of success and second, propose a comprehensive framework for future cross-national research on IS success in multinational organizations. After the introductory section, the four main components of the proposed framework and their interrelations are presented: IS success, culture, IS standardization, and IS built-in success assumptions. The chapter concludes with the presentation of the new framework.