A number of problems of strategic priorities of development of the enterprises and depressive regions and a contradiction of approaches to strategic sustainability of the enterprises of regions are considered. The need of transfer of emphasis on strategic priorities of development of the enterprises and their innovative component is proved. The errors of target priorities of the modern enterprises are shown. A number of proposals on change of situations in depressive regions is given: 1) on the basis of development of the integrated interregional system of knowledge transfer, innovations, experience and interregional cooperation on the basis of the ministries of the Russian Federation and application of new digital models; 2) applications of strategic digital models of scenario management of development of the enterprises of big, medium and small business and assessment of their full economic results and efficiency.