Entrepreneurial orientation (EO) and sustainable innovation (SI) are critical for the growth of enterprises. This paper presents the first systematic literature review to examine the relationship between EO and SI, providing a comprehensive framework to understand this relationship and identify mediating and moderating factors. The study aims to clarify the current context of literature about the relationship between EO and SI, particularly in the context of sustainability. This systematic literature review is a synthesis of 64 quantitative studies published in Scopus and Web of Science, and the review process was based on the concepts, theories, and investigated relationships within these studies. The findings highlight that research on the EO-SI relationship in the context of sustainability is still nascent, despite growing scholarly interest. Current studies tend to focus on output factors rather than exploring antecedents and other factors influencing this relationship. The review has identified several research gaps and suggested needs for studies on mediating and moderating variables, longitudinal research, and research in developing countries.