Striatin (STRN) is a multifunctional scaffold protein that has emerged as a key regulator in both cardiovascular disease (CVD) and cancer. Through modulation of kinases, phosphatases, and calcium-dependent pathways, STRN plays a pivotal role in maintaining cell signaling. In CVDs, STRN role is mediated via STRN influence on vascular reactivity, blood pressure regulation, and vascular remodeling. Moreover, STRN polymorphism has been linked to salt sensitivity of blood pressure. At the same time, the STRN role in tumor progression has been documented across multiple cancers, primarily through its fusion with proteins such as anaplastic lymphoma kinase (ALK), or increased STRN expression. The STRN-ALK fusion has been documented to drive oncogenesis in lung, thyroid, and several other cancers. This review synthesizes current findings on the STRN dual role in cardio-oncology, highlighting its molecular mechanisms and potential therapeutic implications. However, additional research is required for a deeper understanding of STRN-mediated signaling, which may lead to the development of novel biomarkers for interventions in cardio-oncology.