The problem of efficient management of municipal solid waste (MSW) flows remains one of the most urgent environmental and socio-economic problems of the Ukrainian regions. Ineffective MSW management leads to a significant negative impact on the abiogenic and biogenic components of the environment, as well as on the Ukrainian regions' citizens' state of health. Each individual region has its specific situation that should be taken into consideration for the development and implementation of regional plans for MSW management. Usually most of these regional plans are limited by such factors as determination of the volume of generated MSW, inventory of landfills, calculation of the required number of containers and technical means, justified expediency of MSW sorting stations placement, new MSW landfills construction etc. However, little attention is paid to introduction of innovative approaches for development of an effective MSW management system. There is no systematic approach to solving the MSW-related problem and all efforts aim at eliminating the consequences, rather than changing the ultimate cause. The aim of the research is to assess the prerequisites for the formation and implementation of a MSW management plan in Odesa Region from a systematic approach perspective. The methodological basis of the research includes analysis of the existing regulatory and legislative framework in the area of regional MSW management. The work is based on the relevant published data, materials of the Draft Regional Waste Management Plan in Odesa Region by 2030, as well as the results of our own research activities. The regional MSW management plan can be implemented at the following main areas: introduction of a MSW management system in big cities (separation of easily-decomposed organic fraction and hazardous waste, creation of recycling centre and stations etc.); landfill activities (construction of waste sorting plant, construction of biochemical processing/composting facilities, biogas production); development of logistics services (transition to small garbage trucks: separate vehicles for individual MSW components or vehicles with separate sections without waste precompaction); training of qualified personnel, educational work with great masses of population. Consideration of these prerequisites during the formation and implementation of a MSW management plan in Odesa Region will help to increase the environmental safety of the population, reduce the negative impact on the environment through improvement and modernization of the existing MSW management system and achievement of the final "zero waste" condition after conversion of the maximum waste amount into liquid secondary raw materials, alternative energy source and environmentally friendly organic mineral fertilizer. The implementation of the conceptual and theoretical foundations for formation of an optimized MSW management system will contribute to the achievement of the goals of sustainable development set by Odesa Region.