The article is dedicated to detecting the features and the priority directions of implementing a comprehensive state program of import substitution in the mechanical engineering industry of the Russian Federation. Based on the analysis of statistical data on the state of the productive capacity of the machine-building complex of the Russian Federation, the author found that there are necessary conditions and possibilities for solving complex problems of modernization and ensuring the rapid development of the domestic engineering industry in the Russian economy. It is proved that implementing these goals should be based on an effective state program of import substitution corresponding to the modern conditions and capable of ensuring the integrity and diversity of the process of transformation. The need for using program and target methods is defined by the state importance of the problem of ensuring the intensive and advancing development of the domestic engineering industry, the existence of an urgent need for a solution of the considered problem by system strategic methods within a uniform plan, a need for expeditious development and taking measures aimed at improving the legislation of the Russian Federation in the spheres of industry, customs and tariffs, fiscal, social, and educational policies taking into account the time aspect; receiving social and economic effect. The purpose of a comprehensive state program of import substitution in mechanical engineering is proved, the conditions for its successful implementation and the expected results are determined.