In the context of the city of Medellín (Colombia), which has been declared a National Science, Technology, and Innovation District, Knowledge Management Practices (KMPs) have been gaining importance because they improve the commercial entrepreneurial ecosystem by articulating tacit and explicit knowledge. The study investigates the role of KMPs in Social Entrepreneurship (SE), and how this relationship generates products and services that meet social needs, with articulation between tacit and explicit knowledge, which start from the experiences of entrepreneurs and join shared interests in ecosystems and public policies of social entrepreneurship. This study employs a non-experimental design based on a survey and a deep interview for 40 SE initiatives; we then developed a Pearson’s bivariate correlation review and a narrative design. The results reveal that SE initiatives aimed at novel market niches and management strategies that articulate multiple sectors and social actors that aim for a practical scope of the purposes of entrepreneurship concerning the 2030 Agenda of the United Nations. The findings of this study suggest that KMPs in SE create a series of perspectives that seek to achieve greater competitiveness and sustainability in front of the market, all from innovative proposals of social value articulated with environmental care.