Recent findings on some unsolved powder rheology problems and new challenges regarding mechanochemical powder processing and flow modelling are presented. There is remarkable difference in rheology when processing moist powders in static or dynamic conditions. Despite of regular trends of shear stress changes with humidity found in the both cases, some exceptions revealed the significant impact of particles size and their hygroscopic nature as example. Mechanochemical methods of high-energy interactive mixing of highly cohesive powders doped with nano-sized solid admixture enabled their flowability to be improved considerably. Using statistical approach, more general routine is proposed that allow the optimal mixing parameters to be reliably predicted with limited number of experiments needed. Ability to flow of some hygroscopic powders was examined with DEM method and extreme sensitivity of model output to input particle properties was found. The common DEM routine towards powder flow prediction is therefore suggested to be replaced with approach featuring in using DEM method to identify some unknown powder flow factors.