The paper presents the results of a study on the development and application of methodological tools for an integrated assessment of how a large-scale infrastructure project impacts the economy of a region and the country. The methodological basis of the paper is a combination of two major areas of analysis and evaluation of the efficiency of projects: project analysis techniques and methodological approaches to studying the economy in the spatial and sectoral profiles using the optimization multiregional input–output model (OMIOM). The combination of these areas makes it possible to evaluate the indirect effects of a project and obtain results for the main macroeconomic indicators at the national and macroregional levels. For the first time, the paper presents the results of calculations with the proposed approach to evaluating the public efficiency of infrastructure projects based on a real project with reliable information. The impact of the Eastern Siberia–Pacific Ocean-2 project on the economy of the Russia and the Far Eastern Federal District is comprehensively assessed taking into account the redistribution and indirect effects from implementation of the project.