This study attempts to conceptualize the direct implications of entrepreneurial orientation and knowledge management on innovation performance and seeks to determine the mediation effect of marketing orientation on these relationships. This is the first attempt to construct such a model. The study empirically examines the conceptual model using a sample of 221 CEOs and owners of Small and Medium Enterprises (SMEs) in Kuwait. The data was collected using a close ended self-administered questionnaire. The validity and reliability of the model is tested using a measurement model and the structural model is constructed to understand the significance of the conceptual relationship posited in the hypotheses of the study. The findings of the study indicate that entrepreneurial orientation and knowledge management had a considerable effect on innovation performance and that marketing orientation had a considerable influence on innovation performance. In addition, the findings indicate that marketing orientation mediated the effect of entrepreneurial orientation and knowledge management on innovation performance. This study has provided some empirical evidence for the importance of entrepreneurship and innovation as well as knowledge management in ensuring the success of SMEs; it also provides an explanation on the manner in which entrepreneurial orientation and knowledge management improve the innovation performance of SMEs.