VULNERABILITY AND RESILIENCE of urban waters, under the shifting paradigm of climate change and urbanization, needs to be evaluated from both quantitative and qualitative perspectives. We evaluated the vulnerability of urban waters of Guwahati, the largest city in Northeastern India, and Colombo, the coastal National Capital Territory of Sri Lanka, by analyzing the concurrence of Pharmaceuticals and Personal Care Products (PPCPs), enteric virus, antibiotic resistant bacteria (ARB), metal, faecal contamination and antibiotic resistance genes (ARGs), as well as long-term changes in precipitation and temperature. Escherichia coli (E. coli) ranged from 10-27 cfu ml-1 in the Kelani river, and from below detection limit to 49 cfu ml-1 in the Brahmaputra. E. coli strains isolated from the water were evaluated for resistance to the antibiotics norfloxacin, ciprofloxacin, levofloxacin, kanamycin monosulphate, tetracycline and sulfamethoxazole. In both countries, most of the isolates were resistant to multiple drugs and the resistance was greater for older generation antibiotics. The Brahmaputra River showed greater resistance to all of the antibiotics than the Kelani and Gin rivers. Antibiotic resistance genes gyrA, tetW, sul1 and ampC were detected in the Kelani River, while aac-(6’)-1b-cr, gyrA, tetW, sul1, ampC and blaTEM were detected in the Brahmaputra River. Antibiotic resistance appears to be not correlated with the prevalence of PPCPs and E. coli, but with anthropogenic pollution and lifestyle. CSIRO and MIROC models predict more than a 1.2 °C increase in average yearly temperature, whereas average yearly precipitation is likely to remain the same, with some abnormalities in high and low extremes. A resilient framework is needed that ensures participation of every stakeholder by defining specific roles in the implementation process.