The necessity for sustainable development, the coronavirus pandemic, and conducting business within the frameworks of the fourth industrial revolution—Industry 4.0 create a challenging environment where enterprises have difficulties to achieve and maintain competitiveness. Information is becoming a core construct when it comes to conducting business in the modern, globalized business environment. In this paper, the influence of information systems (IS) on sustainable business performance and competitiveness is analyzed. Additionally, the influence of human resource management (HRM) and decision making (DM) on sustainable business performance and competitiveness, as two crucial constructs in the new paradigm of conducting business, are addressed. The relations are discussed from the aspect of sustainable development and future post-pandemic business trends. The main goal is to determine the relations between the noted constructs in a transitional setting. In sum, 184 manufacturing enterprises from Republika Srpska were surveyed via a structured survey, where the focus was on quantifying and modeling the influence of IS, HRM, and DM on sustainable business performance. The results indicate that IS, HRM, DM can affect business performance in a transitional economic setting. This approach is novel, as the existing body of literature does not address all the noted influencing factors on sustainable business performance and competitiveness in a transition economy. Hence, this paper significantly contributes to the existing body of literature and provides a solid basis for future research in this domain.