This empirical research explores the links between customized marketing, improved customer support, business efficiency, competitive advantage, and adaptation to market trends towards the online business of small and medium-sized enterprises. The research goal was a deeper understanding of the relationships between the mentioned independent and dependent variables. The study aims to provide a comprehensive understanding of how these variables influence medium-sized enterprises online business success. The methodology includes analyzing data collected through surveys among 232 respondents from small and medium enterprises from the territory of the Republic of Serbia. Different analysis methods were used, statistical test analysis of variance, multiple correlation analysis of variables and to confirm the hypothesis multiple regression analysis, as well as qualitative analysis, to identify the key factors of online business of small and medium enterprises. Qualitative analysis complements these methods by identifying pivotal factors impacting small and medium-sized enterprises online business strategies. The results of the research indicate a significant positive and strong impact of customized marketing, improved customer support, business efficiency, competitive advantage, and adaptation to market trends towards the online business of small and medium-sized enterprises. Also, it was found that the online business of small and medium-sized enterprises can be explained directly through improved customer support at 54.76%, business efficiency at 46.24%, customized marketing at 44.89%, adaptation to market trends at 34.81%, and competitive advantage at 16.00%. By monitoring consumer and industry trends, small and medium-sized enterprises can adjust strategies and offerings to meet evolving customer needs, fostering revenue growth and expanding market presence. These studies contribute to the theoretical understanding of the online business of small and medium-sized enterprises.