Based on a systematic approach, the article examines the main macroeconomic global and national challenges in the development of the domestic agro-industrial complex that affect the sustainable development of the industry and the achievement of national development goals of the Russian Federation. It is shown that the identification of the main challenges facing the development of the domestic agro-industrial complex is the primary basis for developing goals for the strategic development of the agrarian sector. In the work, on the basis of a complex of sources, the main global challenges are identified: demographic growth and hunger; lack of resources within the framework of the existing AIC3.0 model; ethical restrictions and risks; growing threats of the spread of dangerous infectious diseases; natural and climatic changes; external geopolitical and sanctions pressure. National barriers are also identified: lagging behind developed countries in the process of transition to a new technological order; import dependence in the context of growing external restrictions and challenges for Russia; food waste and product losses at the storage, processing and logistics stages; value restrictions; socio-physiological factors. Responses to these challenges and limitations are the basis a new model of economic development of the Russian agro-industrial complex.