Artificial organs, such as extracorporeal membrane oxygenators, dialyzers, and hemoadsorber cartridges, face persistent challenges related to the flow distribution within the cartridge. This uneven flow distribution leads to clot formation and inefficient mass transfer over the device’s functional surface. In this work, a comprehensive methodology is presented for precisely integrating triply periodic minimal surfaces (TPMS) into module housings and question whether the internal surface topology determining the flow distribution affects blood coagulation. Three module types are compared with different internal topologies: tubular, isometric, and anisometric TPMS. First, this study includes a computational fluid dynamics (CFD) simulation of the internal hemodynamics, validated through experimental residence time distributions (RTD). Blood tests using human whole blood and subsequent visualization of blood clots by computed tomography, allow the quantification of structure-induced blood clotting. The results indicate that TPMS topologies, particularly anisometric ones, serve as effective flow distributors and significantly reduce and delay blood clotting compared to conventional tubular geometries. For these novel TPMS modules, the inner surfaces can be activated chemically or functionalized to function as a selective adsorption site or biocatalytic surface or made of a permeable material to facilitate mass transfer.