Abstract <p>The article presents a review of the results from the study of genetic-demographic processes in the populations of three largest Russian megalopolises, Moscow, St. Petersburg, and Novosibirsk, and the capital of the Republic of Belarus, Minsk. The main genetic-demographic parameters of the megalopolis residents were calculated from survey and population censuses. Data on population migration and marriage structure parameters are provided. The results of the analysis of uneven ethnic group settlement and assessment of ethnic diversity, as well as sample maps reflecting ethnic topography of the megalopolis population are presented. In the male population of the studied megalopolis, Y-chromosome haplogroup distribution patterns in association with migration processes are revealed. The need to create genetic databases, as well as reference databases for the purposes of medical genetics and forensic science is substantiated, taking into account the complexity and dynamism of the megalopolis population structures under the influence of genetic-demographic processes.</p>