This conceptual paper focuses on the Agro-Food Hub paradigm as the main enabler for the sustainable development of agro-food Small and Medium Enterprises (SMEs) in the context of the currently established agro-food systems. This paper is based on a shared knowledge-driven research that presents different approaches/types of Agro-Food Hubs, providing useful insights into the strategic, operational and institutional approaches of the topic. After the illustration of the main approaches for the Agro-Food Hubs met in the literature, a holistic Agro-Food Hubs model was proposed (the Agro-Food Sustainability Knowledge Hub model), incorporating the main principles and functional guidelines within the framework of the Corporate Social Responsibility (CSR) and Sustainable Supply Chain Management. This study is in line with the demographic, economic and social prospects for the 2050 and the European Economic and Social Committee decision for “An EU Industrial Policy for the Food and Drinks Sector„ adopted on 4 May 2015. In particular, since the majority of research in the past focused on large organizations, this paper is expected to enlighten the problems emerged from current applied practices together with the opportunities for potential synergies among agricultural SMEs, through the utilization of alternative sustainable channels of distribution and value creation, such as the Agro-Food Hubs.