In the article modern tendencies of transnationalization of business activity in large cities of Ukraine are analyzed. The factors of its activation at this stage of development of the postindustrial society are determined. The modern tendencies of the development of the most powerful transnational corporations (TNCs) are determined on the basis of the review of the top 500 largest TNCs, the list of top 10 world-multinational corporations has been formed. Based on the review of components of the Transnationalization Index at the national, corporate and local levels, it was concluded that the methodological base and the low level of provision of statistical data for urban economic development are inadequate to calculate the Corporate Activity Index for large cities with TNK’s branches and headquarters. It has been established that the processes of transnationalization of the Ukrainian economy are developing asymmetrically: they are characterized by the penetration of foreign TNCs into the country, and the formation of domestic transnational companies is slow. The peculiarities of development of foreign affiliates in Ukraine by types of economic activity, place of localization, corporate social responsibility are revealed. The advantages and disadvantages of transnationalization of urban economies in the context of modernization of TNCs in Ukraine are estimated. The analysis of transnationalization of business activity of cities of Ukraine on the example of the cities of Kyiv, Vinnytsia, Lviv, and Kharkiv by indicators of foreign direct investment inflow, the localization of branches of foreign TNCs, and the availability of strategic goals for the enhancement of international cooperation in urban development strategies have been analyzed. An increase in foreign revenues has been set for the economy of cities during 2015-2018, but the offshore countries dominate in structure of FDI by countries of investment, which testifies to efforts to minimize taxation. The analysis of investment activity showed uneven distribution of volumes of investment flows between cities, areas of interest of TNCs and local priorities of investing in the urban economy. The author also reveals that with the same strategic planning of cities development regarding the importance of international cooperation, there are different models of attracting the attention of a private foreign investor and various local regulatory mechanisms (administrative, tax, marketing, personnel, etc.). Conclusions were made on the feasibility of developing TNC tax regulation tools at the local level to develop measures to defeat the investment climate. Proposals on the introduction of mechanisms for regulating the activities of foreign TNCs in the legal, economic, social spheres are developed. The possibilities of stimulating the creation of domestic international corporations and the possibilities of state regulation to minimize risks and achieve strategic goals of increasing the competitiveness of cities are revealed. The approaches to implementation of the instruments of regulation of the large cities’ economy transnationalization in Ukraine are proposed, the implementation of which should help improving the business environment, adapting the urban economy to the features of the global economy and increasing its investment attractiveness.