<p>Cardiorenal syndrome denotes a complicated interaction in which abnormalities in one organ, the kidneys or the heart, cause abnormalities in the other, resulting in severe co-morbidities and a higher risk of death. Developing successful treatment plans requires understanding the molecular underpinnings of this reciprocal connection. According to recent studies, non-coding RNAs, particularly microRNAs, are essential modulators of gene expression in the setting of renal and cardiovascular disorders within CRS. This review summarizes the current knowledge about the functions of ncRNAs and the transforming growth factor-β signaling pathway in CRS, as well as how ncRNA dysregulation affects essential functions such as endothelial integrity, oxidative balance, and fibrotic responses in the kidneys and heart. Particular miRNAs that impact exosomal and mitochondrial pathways and have potential as diagnostic biomarkers for CRS subtypes and phases are highlighted. The pathophysiology of ischemia injury also demonstrates the relationship between exosome miRNAs and cell-to-cell communication. The reciprocal relationship between TGF-β signaling and ncRNA production is further clarified in the review, which also examines how this interaction may be involved in the maladaptive remodeling feature of CRS. Alongside a discussion of the challenges in translating these discoveries into effective treatments, an assessment of contemporary therapeutic approaches, such as volume management techniques and targeted molecular interventions, is provided. The significance of ongoing research on ncRNA-TGF-β in CRS is emphasized in this review, along with the potential for developing innovative diagnostic and treatment approaches that consider the complex interactions between the kidneys and heart in this debilitating condition.</p>