<p>Chemotherapy and immunotherapy are now both crucial methods for combating cancers. However, the interplay between immunotherapy and chemotherapy is highly intricate, and varying combinations and sequencing of treatment may produce distinct therapeutic outcomes. Chemotherapy, with its cytotoxic effect, may trigger immunogenic cell death and alter the tumor microenvironment, hence affecting immune responses. On the other hand, immunotherapy may potentially enhance the effectiveness of chemotherapy by eliminating cancer cells via the stimulation of the immune system. This article focuses on the effect of treatment sequence on efficacy, which is less systematically discussed in the current literature. We deeply analyzed the synergistic potential of chemotherapy and immunotherapy and explored how these two modalities can enhance each other to improve treatment efficacy. By summarizing the latest research results, we elucidated their interaction mechanisms and emphasized the potential advantages of sequential treatment. Integrating these insights aims to provide clinicians with novel therapeutic concepts, consequently optimizing therapy strategies and augmenting the prognosis for cancer patients.</p> Graphical abstract <p></p>