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An essential task for operation and planning of biogas plants is the optimization of substrate feed mixtures. Optimizing the monetary gain requires the determination of the exact amounts of maize, manure, grass silage, and other substrates. For this purpose, accurate simulation models are mandatory, because the underlying biochemical processes are very slow. The simulation models may be time-consuming to evaluate, hence we show how to use surrogate-model-based approaches to optimize biogas plants efficiently. In detail, a Kriging surrogate is employed. To improve model quality of this surrogate, we integrate cheaply available data into the optimization process. To this end, multi-fidelity modeling methods like Co-Kriging are applied. Furthermore, a two-layered modeling approach is used to avoid deterioration of model quality due to discontinuities in the search space. At the same time, the cheaply available …