One third of the global carbon emissions are emitted by the building sector. Over the last decades, space heating loads have decreased in modern buildings, and domestic hot water (DHW) is now oftentimes the largest energy consumer in the household. We developed the WaterHub modeling framework to assess the potential of technologies or measures targeting DHW energy demand. The framework combines process-based technological models and stochastic water demand modeling in a modular way to allow for holistic simulations of complex DHW systems. In two rigorous tests of the modeling framework, we demonstrated the importance of water consumption dynamics in the modeling of DHW systems, showing that static modeling leads to underestimated heat losses and wrong energy consumption predictions. In an exemplary case study, we identified and quantified the synergistic interactions between water boiler temperatures and a drain water heat recovery device, demonstrating the strength of this methodology for optimizing strategies targeting DHW systems. With its modular structure, this open-source modeling framework can be extended to include any DHW-related technology, providing a useful common platform for collaboration between technology developers and water experts.