Polygeneration systems have been shown to be a flexible arrangement which can meet seasonal product demands for electric power, fuels and chemicals. This is especially relevant for small markets such as isolated small-medium size communities demanding electricity, and fuels. This work is focused on the feasibility of a polygeneration system based on a single-step DME plant to produce 200,000 tonnes/year of DME and 200 MW of electricity. An economic analysis is carried out to assess different configurations and feedstocks for syngas production. The DME-production was simulated at different possible recycle ratios and under the condition of potentially reduced catalyst performance. In all cases, the once-through polygeneration system showed significant improvement over all other configurations e up to 11.6% reduction in the amount of synthesis gas required to produce DME and power e with a corresponding reduction in “wasted” feed leaving as effluent CO2. The flexibility of an integrated system meant that, in cases of decreased catalyst activity or selectivity, the advantages of the integrated system over standalone configurations are even greater e up to 18.6%. Moreover, polygeneration systems show further economic advantages depending upon the selling price of electricity for both fossil fuel and biomass sources of the syngas feedstock.