Secondary settling tanks (SSTs) are a very crucial process that determines the performance of the activated sludge process (ASP). Due to the importance of its performance, computational fluid dynamics (CFD) models have been employed for the designing new SSTs, the modifying the geometries of existing SSTs and improving control techniques in wastewater treatment plants. However, the practical application of SST CFD models remains challenges due to several difficulties, such as the uncertainty of model structures and the accuracy of different sub-models. To facilitate the practical application of CFD SST models, this dissertation focuses on the numerical analysis of SST models, including the evaluation of different turbulence sub-models and investigation the impact of different parameters in modeling structures and the application of CFD models on the design and operation of SSTs, including improving the understanding the effects of different operation parameters, and surface wind conditions on the performance of SSTs. To improve the understanding of CFD modeling of SSTs, this dissertation provides a comprehensive literature review of different multiphase approaches and the widely applied single-phase approach to model the motion of the particle in SSTs. The literature review also provides a thorough introduction of current CFD research and engineering practice, focusing on the formation and the effect of density currents, effects of different design variables, parameter uncertainties in modeling structures and atmospheric conditions. Also, the widely applied standard k- (SKE) turbulence sub-model is investigated with two more advanced turbulence models (RNG k- and Realizable k- models). The results show that turbulence sub-model selection has a strong influence on the prediction of hydrodynamics of an SST, especially inside the inlet zone, and on the prediction of flow capacity. Moreover, due to the inconsistency of coupling or decoupling the buoyancy-term in the turbulence model structure among different studies as well as the discrepancies observed in other modeling structures, including in the sludge transport model, sludge settling model, dry solids density and different inlet turbulence boundary conditions, their impact on the prediction accuracy of an SST are all investigated. This dissertation also investigates CFD applications on the design and operation of SSTs, including improving the understanding of the effects of different operation parameters, and surface wind conditions on the performance of SSTs. The effects of different operation parameters, such as surface overflow rate (SOR), sludge loading rate (SLR), the concentration of mixed liquid suspended solids (MLSS), and returned activated sludge (RAS) concentration, are firstly evaluated with professor McCorquodale's Quasi-3D SST model. Next, the operational strategy to these operating parameters is investigated with Ansys Fluent-based model in order to maximize the SST capacity. The maximum capacity predicted by the Fluent-based CFD model is then compared with the prediction of one-dimensional idealized flux theory (1DFT) model. Also, the performance of the McKinney baffle on the SST performance is evaluated and shows significant improvement on the SST performance. Finally, instead of focusing on the influential factors inside SSTs, the effects of wind on the performance of both circular and rectangular SSTs are studied. Due to the strong negative impact of wind on the SST performance, the prediction results suggest that in strong windy climates covering SSTs or protecting them from strong winds may be justified.