The concept of interdisciplinarity has been the focus of much reflection, but studies on the implementation of interdisciplinarity in secondary schools remain rare. This literature review aims to provide a state of the art empirical studies of interdisciplinarity in secondary schools. This systematic review, based on PRISMA standards, includes a descriptive analysis and a thematic analysis using inductive and deductive methods. Studies were identified using the following databases, Web of Science (WOS), Taylor & Francis (T&F), ERIC, and Science Direct (SD). A total of 40 studies were selected and analyzed to: (1) provide an overview of interdisciplinary practices in secondary schools; (2) highlight the effects of interdisciplinary practices on teachers and students; and (3) identify the conditions that favor the construction of interdisciplinary sequences. The results of this review show that few interdisciplinary practices are used in secondary schools and that even fewer achieve a real integration of disciplines. Interdisciplinary approaches seem to have positive effects on both students and teachers (promoting learning and, interest, developing interpersonal skills and encouraging professional development) when it is possible to overcome the many obstacles they face and to implement them in favorable conditions, such as those featuring a strong conceptual link between disciplines or complementarity between disciplinary and interdisciplinary moments.