Inequality in water allocation and the shortage of water resources are two of the main critical components of multi-regional water system management. The impact of virtual water flows implied in inter-regional trade on multi-regional water resources issues is often ignored, especially on issues as complicated as water quality-based and water quantity-based issues. Therefore, a multi-region blue/grey water management system is developed in this study with a detailed case study of the Yangtze River Economic Belt (YREB). In detail, both blue water footprint (BWF) and grey water footprint (GWF) are considered in the proposed model. And the virtual water flows inherent in inter-provincial trade are quantified using a multi-regional input-output analysis. Based on this, the blue water and grey water metabolic systems are next assessed respectively in terms of system health state, regional resource inequality, and the water scarcity. In particular, the impact of virtual water transfers is also innovatively examined in this context. It shows that water pollution affects most of the YREB provinces (Shanghai (SH), Jiangsu (JS), Anhui, Hubei, Yunnan, Jiangxi). And SH and JS suffer from shortages of available water, with the water availability scarcity index for both provinces being above 0.4 during the study period. The transfer of virtual blue water (BW) exacerbates overall BW inequalities while alleviating water availability shortages in most provinces (except SH, Zhejiang, Chongqing, Sichuan). Differently, the transfer of virtual grey water (GW) has a mitigating effect on overall GW inequalities. And it has the highest impact on SH's water quality shortage, with a virtual grey water transfer impact coefficient of 23.64 in 2007. The findings provide a new pathway for coordinated water management intra- and inter-provinces, as well as a reference for the development of multi-regional water management policies.