Uncertainty is a central concept in the decision-making process, especially when dealing with biological systems subject to large natural variations. In the design of activated sludge systems, a conventional approach in dealing with uncertainty is implicitly translating it into above-normal safety factors, which in some cases may even increase the capital investments by an order of magnitude. To obviate this problem, an alternative design approach explicitly incorporating uncertainty is herein proposed. A probabilistic Monte Carlo engine is coupled to deterministic wastewater treatment plant (WWTP) models. The paper provides a description of the approach and a demonstration of the general adequacy of the method. The procedure is examined in an upgrade of a conventional WWTP towards stricter effluent standards on nutrients. The results suggest that the procedure can support the decision-making process under uncertainty conditions and that it can enhance the likelihood of meeting effluent standards without entailing above-normal capital investments. The analysis led to reducing the capital investment by 43%, producing savings of more than 1.2 million euro.