The article discusses the economic and managerial issues of modeling domestic innovation in industry. The linear and nonlinear modeling of innovation is disclosed. The stages of the innovation life cycle are investigated, the structure of innovative projects is considered, the procedure for selecting innovative projects is proposed, the selection scheme is presented, which is the basis for modeling technical complexes and technological activities for various purposes. The theoretical aspects of modeling, the practice of organizing modeling on the example of the Samara region are considered. To solve the problems of developing the economy of the Samara region, a comprehensive transition to the path of innovative development and the creation of a knowledge-based economy is necessary. The model of innovative development of the industrial complex of the region proposed by the author integrates the efforts of state authorities and industrial business in the formation and development of high-tech clusters. It follows that the priority task in this area is the creation of a new regional innovation system. The most significant result of the work is the proposal to organize a cluster model of innovative activity in the region, to create a cluster innovation infrastructure. It is noted that the innovative model for the development of industry in the region must be built using the innovative potential of industrial clusters, as well as on the basis of clusters to form the innovative infrastructure of the region. Clusters, having a significant innovative potential in their structure, diffuse innovations into other economic systems of the region. For this purpose, the author proposes to create an innovation development center in the cluster in order to coordinate innovative activity of both enterprises resident in the cluster and other industrial structures of the region. A mechanism is proposed for implementing the model of innovative development of the region, in which system benchmarks are set by the levels of resource, industrial, investment and innovative potentials of the region. Based on a comprehensive analysis of the region’s potential and “growth poles” for the development of innovative activity, the parameters of innovative development are compared with the criteria base.