The article is devoted to the study of the regional socio-economic systems' reactions to changes in national macroeconomic parameters. The features of the agro-industrial regions' economy and social sphere adaptation are revealed. The main problems of the development of agro-industrial regions, characterized by peripheral position, are disclosed. The characteristic of restrictions, risks and threats to their development is given. On the example of the Altai Territory, an attempt to comprehensively consider key challenges to the development of the region.
 In the field of economics, the following are identified as threats:
 — de-industrialization of the region economy;
 — limited reproductive capabilities;
 — a significantly deeper fall in labor productivity compared with Russia;
 — lack of conditions for ensuring modernization and qualitative changes in the region economy.
 The three most acute problems in the sphere of population incomes are outlined: low income level; insufficient growth rates; poverty and excessive income inequality.
 The most important demographic risks of the sustainable development of the Altai Territory are revealed: population reduction, aging, and imbalances in resettlement.
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