<div>Physical phenomena in nature are typically represented by complex systems of ordinary differential equations (ODEs) or partial differential equations (PDEs), modeling a wide range of spatio-temporal scales and multi-physics. The field of computational science has achieved indisputable success in advancing our understanding of the natural world - made possible through a combination of increasingly sophisticated mathematical models, numerical techniques and hardware resources. Furthermore, there has been a recent revolution in the data-driven sciences - spurred on by advances in the deep learning/stochastic optimization communities and the democratization of machine learning (ML) software.</div><div><br></div><div><div>With the ubiquity of use of computational models for analysis and prediction of physical systems, there has arisen a need for rigorously characterizing the effects of unknown variables in a system. Unfortunately, Uncertainty quantification (UQ) tasks such as model calibration, uncertainty propagation, and optimization under uncertainty, typically require several thousand evaluations of the underlying physical models. In order to deal with the high cost of the forward model, one typically resorts to the surrogate idea - replacing the true response surface with an approximation that is both accurate as well cheap (computationally speaking). However, state-ofart numerical systems are often characterized by a very large number of stochastic parameters - of the order of hundreds or thousands. The high cost of individual evaluations of the forward model, coupled with the limited real world computational budget one is constrained to work with, means that one is faced with the task of constructing a surrogate model for a system with high input dimensionality and small dataset sizes. In other words, one faces the <i>curse of dimensionality</i>.</div></div><div><br></div><div><div>In this dissertation, we propose multiple ways of overcoming the<i> curse of dimensionality</i> when constructing surrogate models for high-dimensional numerical simulators. The core idea binding all of our proposed approach is simple - we try to discover special structure in the stochastic parameter which captures most of the variance of the output quantity of interest. Our strategies first identify such a low-rank structure, project the high-dimensional input onto it, and then link the projection to the output. If the dimensionality of the low dimensional structure is small enough, learning the map between this reduced input space to the output is a much easier task in</div><div>comparison to the original surrogate modeling task.</div></div>