Abstract The potential of polygeneration systems, in terms of profitability, energy saving and pollutant emissions reduction, highly depends on several factors such as plant efficiency, local normative and tariff conditions and reference technologies adopted to compare the results. In Part I of this paper a reliable tool was described, capable of optimizing the lay-out, design and operation of an integrated polygeneration system serving a cluster of buildings with their heat, cooling and power demand; the tool represents an excellent instrument to perform sensitivity analyses, thus enabling the analyst to formulate general design criteria and predict the effects of any change in the boundary conditions or in the normative provisions concerning support mechanisms for polygeneration plants. In this Part II of the paper, with reference to a cluster of four buildings located over a small area, once assumed a fixed topology of the site (in terms of distance between buildings) the sensitivity of plant design and operation is investigated, posing a particular focus on some context conditions: (1) the minimum primary energy saving imposed for the “high efficient cogeneration” assessment, (2) the reference efficiency of “separate power production” systems adopted to evaluate energy savings, (3) the local energy prices and (4) the incidence of tax exemption for the fuel consumed by polygeneration plants. The sensitivity analyses are preceded by an accurate study on the robustness of solutions, performed by assuming different widths of the temporal basis adopted for the optimization. The proposed study offers a comprehensive view and interesting insights as concerns the viability of polygeneration systems for buildings applications.