Computational fluid dynamics (CFD) can inform sustainable design of buildings and cities in terms of optimizing pedestrian wind comfort, air quality, thermal comfort, energy efficiency, and resiliency to extreme wind events. An important challenge is that the accuracy of CFD results can be compromised by the large natural variability and complex physics that are characteristic of urban flow problems. In this talk, I will present an investigation of the potential of large-eddy simulations (LES) towards predicting peak wind pressure loads on high rise-buildings. First, the sensitivity of LES results to the turbulence in the incoming boundary layer wind is quantified and the results are validated against wind tunnel experiments. Next, high resolution LES are employed to gain a better understanding of the flow physics that govern small-scale extreme suction events observed in specific locations on the façade. Finally, a multi-fidelity simulation strategy, aimed at reducing the overall computational cost of LES-based cladding load predictions, is explored. The talk will conclude with an overview of ongoing work on full-scale wind pressure measurements on high-rise buildings for future validation and uncertainty quantification studies.