Dilated cardiomyopathy (DCM) is the most common cardiomyopathy worldwide. Over the last few decades, significant progress has been made in understanding the genes responsible for DCM. A large number of variants have been detected, with heterogeneous distribution across the globe. Based on a systematic review of the available data, this review aims to investigate what we actually know about genetic, geographical and ethnic heterogeneity in DCM. What emerged is a disparity in clinical and instrumental valuations across different populations. Given the significant variability in the clinical and molecular presentation of these diseases, there is a need to develop an operational model that integrates technical and molecular diagnostics, imaging, and clinical capabilities tailored to the characteristics of different territories, while accounting for migratory flows and sex differences. By characterising specific genotypes, we could offer targeted therapies or contribute to the development of new care.