Integrated Water Resources Management (IWRM) is a process which strives towards the sustainable management of water resources in river basins. The approach integrates insights and knowledge from various scientific disciplines comprising natural, socio-economic, and engineering sciences. These three pillars of sustainability are important components of this approach integrating the environmental, economic and social dimension. In the ideal IWRM case planning is based on the river basin scale and therefore is comparatively discussed herein for the two twinning BRAHMATWINN river basins, i.e. the Upper Danube River Basin (UDRB) in Europe and the Upper Brahmaputra River Basin (UBRB) in South Asia. In this chapter major challenges for the implementation of the IWRM process towards a sustainable management of water resources in the two UDRB and UBRB twinning river basins of the BRAHMATWINN project are analysed. The study revealed that in the UDRB the IWRM approach is already part of water management planning and the implementation of the EU Water Framework Directive (WFD) is a good example in this regard. Contrary in the UBRB the implementation of IWRM is just at the beginning phase, only recently is being discussed in the riparian states but has not been implemented in any way so far on the basin scale.