Traditionally used herbal medicines are deep in the consciousness of patients for the treatment of only minor diseases by self-medication. However, manufacturers of herbal medicinal products suffer from major problems such as increasing market pressure by e.g., the food supplement sector, increasing regulations, and costs of production. Moreover, due to more stringent regulation and approval processes, innovation is hardly observed, and the methods used in process development are outdated. Therefore, this study aims to provide an approach based on modern process engineering concepts and including predictive process modelling and simulation for the extraction of traditional herbal medicines as complex extracts. The commonly used solvent-based percolation is critically assessed and compared to the so-called pressurized hot water extraction (PHWE) as a new possible alternative to replace organic solvents. In the study a systematic process design for the extraction of hawthorn (Crataegus monogyna JACQ.) is shown. While for traditional percolation the solvent is optimized to a mixture of ethanol and water (70/30 v/v), the PHWE is run at a temperature of 90 °C. The extracts of various harvest batches are compared to a commercially available product based on a chromatographic fingerprint. For the first time, natural batch variability was successfully incorporated into the physico-chemical process modelling concept. An economic feasibility study reveals that the PHWE is the best choice not only from a technical point of view but also from economic aspects.