Lowvelocities, low pressures, and water stagnation associated with alternating schedules ofsupply and non-supply operation increase the chances of microbial contamination in intermittent waterdistribution systems (WDSs). Chlorination istypically applied to remediate this problem owing to its effectiveness to kill bacteria and viruses,and its ability to provide prolonged free residuals. However, the effectiveness and longevity ofchlorine residual are significantly less in WDSs subjected to the problem of contamination.Chlorination also possesses the dilemma of the formation of carcinogenic disinfection by-products(DBPs). Trihalomethanes (THMs) account for more than fifty per cent of all the halogenated DBPsin WDSs, and they are found to induce carcinogenic and reproductive risks. This research addresses the development of comprehensive models for prediction of microbial and chemical contaminants transport in an Intermittent water distribution system. The conventional hydraulic analysis models consider the distribution pipes as fullypressurized, and they do not significantly detail the filling and emptying phases associated withintermittent operation. Also, all the existing water quality models for WDSs (Eulerian,Lagrangian, and Eulerian-Lagrangian types) are macroscale based, and no effort has yet been made to formulate a mesoscalemodel for representing the physical, chemical, and biological interactions in distribution pipes. Inthis work, an integrated modelling framework is developed using two newly proposed models:PDA-PF and CA-MSRT models. PDA-PF is an improved pressure-dependent analysis model forWDSs, considering both pressurized and partial flow regimes in distribution pipes. CA-MSRTmodel is the first-ever mesoscale water quality model for WDSs developed utilizing the novelRandom Walk Particle Tracking Embedded Cellular Automata approach. The relationships fordefining the reaction kinetics of chlorine decay, natural organic matter (NOM) degradation,microbial decay, and THMs formation during secondary chlorination application are also proposedin the study. The integrated modelling framework is applied to the proposed WDS of the Maduraicity of Tamilnadu, and the best operation practices in terms of chlorine application at the watertreatment plant and at an intermediate engineered booster station are derived. TheAnalytical Hierarchical Process, a multi-criteria decision-making technique, is also employed toderive the chlorine doses which minimize the microbiological and chemical risks at the water outletpoints. Three scenarios of future operation of WDSs are simulated in detail to get a detailed insight into the performance of the developed modelling framework, and the best strategy for operation of the system is recommended.