Studies on entrepreneurship and its impact on economic, political, and social development have increased considerably over the last decade. One of the challenges faced by various countries is the development of companies within the orange economy, which refers to creative and cultural industries with significant potential to generate employment and wealth. Despite this potential, there is a notable lack of empirical research on the factors affecting the management and performance of micro, small, and medium-sized enterprises (MSMEs) within this sector. This study addresses this research gap by examining the influence of reputation, innovation, and knowledge on the performance of MSMEs in the orange economy sector in Colombia. Utilizing partial least squares structural equation modeling (PLS-SEM) to analyze survey data from entrepreneurs, the results reveal that reputation moderates the relationship between innovation and performance, as well as the relationship between knowledge and organizational performance. This study contributes to the literature by providing new insights into the dynamics of creative industries in developing countries and highlighting the essential roles of reputation, innovation, and knowledge in enhancing the performance of MSMEs in the orange economy.