In this study, biogas production from the organic fraction of the MSW (OMSW) was simulated in six different scenarios, using Aspen plus® based on industrial data. The economic evaluations were made using the Aspen process economic analyzer, considering the plant size and the upgrading methods. The base case had an annual processing capacity of 55,000 m3 OMSW. The capital costs and the net present value (NPV) after 20 years of operation were 34.6 and 27.2 million USD, respectively. The base case was compared to the modified scenarios, which had different upgrading methods, processing capacities, addition of biogas from wastewater sludge treatment, and variation of the substrate (OMSW) between ±200 USD/ton. The sensitivity analyses were carried out considering the cost of the OMSW imposed on citizens for collection and transportation of wastes and the different sizes of the plant. The result suggests that producing biogas and selling it, as a vehicle fuel from OMSW is a profitable venture in most scenarios. However, there are some uncertainties, including the collection and transportation costs, landfilling fee, and process operation at lower capacities, which affect its profitability.