Considering the finite volume of fresh water resources, managing its quality and quantity sustainably is one of the greatest challenges because of complex global changes. This work strives to predict the combined effect of urbanization and climate change on water quality in Pasig-Marikina River considering its criticalities to develop proactive plan by policy makers working in water sectors. Pasig-Marikina River is an important source of water for different usage viz. domestic, industrial, agriculture and recreation in the National Capital Region (NCR) in Philippines. However, stationarity of this river basin is compromised by global changes and human disturbances viz., climate change, rapid urbanization and weak/non-structured government policies results in severe pollution, makes long section of the river unsuitable for any use in recent past. Therefore, presenting a comprehensive spatio-temporal status of river water quality using transdisciplinary framework will be valuable to guide and implement better management policies within governance structure. In this study, status of water quality of the Pasig-Marikina River was analysed for current and future timescale using population growth, land use change, wastewater production and treatment scenarios. Water Evaluation and Planning (WEAP) model was used to model river pollution scenarios using three indicators for aquatic ecosystem health viz. Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD) and Nitrate (NO3). Comparison of simulated water quality parameters for the year 2015 and 2030 with 2011 (base year) clearly indicates that the water quality at 2030 will rapidly deteriorate and will be not suitable for any aquatic life in terms of major of water quality parameters. Also, even current existing master plan for wastewater treatment plants and policies are not sufficient enough for sustainable water resource management within NCR, Philippines and hence call for immediate and inclusive action.