Multiple internal conflicts and external emergencies can occur when an enterprise implements a project portfolio (PP), making the PP inevitably deviate from the enterprise’s strategic objectives. As a means of project portfolio change (PPC) that aims to align the PP with strategic objectives, adding new projects can compensate for this deviation. Furthermore, the synergistic relationships in the PP can significantly impact the achievement of the enterprise’s strategic objectives. Therefore, this study presents a procedure for the selection of new projects that considers the synergistic relationships in the PP. First, the deviation between the PP and the enterprise’s strategic objectives is identified. Second, the synergistic relationships between candidate new projects and the projects in the PP are analyzed, based on which a model of new project selection is built. Third, by comparing the model simulation results of the attainment of the strategic objectives of several PPs, the new projects that can best achieve these strategic objectives are added to the PP. This procedure is illustrated using a numerical example showing its applicability and efficacy. For academia, this study provides a theoretical framework for the selection of new projects. Moreover, the straightforward procedure can help manage PPs in business practice.