The naturalness problems of the Standard Model, like the Higgs hierarchy problem, have been some of the most prominent motivations for theoretical particle physics over the last few decades. In the meantime, with technological advances and ingenious search strategies, the experimental measurements, both at colliders and in cosmology, have become much more precise. In this thesis, we discuss innovative ways of using these measurements to study various naturalness-motivated models of new physics. This thesis covers three major research topics. In the first part, we show that the differential cross-sections of Drell-Yan (DY) processes measured at the Large Hadron Collider (LHC) can be used to derive some of the most stringent limits on the parameter space of R-parity violating supersymmetry. We further demonstrate that these analyses are future-oriented, as the indirect limits from DY processes will continue to improve as the LHC accumulates more luminosity, even without any additional energy. In the second part, we derive the most accurate cosmological constraints to date on the Mirror Twin Higgs (MTH) model, a model that contains a near-mirror copy of the SM and is a potential solution to the Higgs hierarchy problem. In addition, we find regions of the model parameter space in which cosmological anomalies in the measurements of the Hubble constant and the matter power spectrum can be explained. Finally, in the third part of the thesis, we explore minimal flavor violating (MFV) scalar leptoquarks as the potential source of the anomaly in the measurement of R_D. MFV is a framework that can lead to a natural flavor structure for new physics models. We show that a MFV scalar leptoquark explanation of the anomaly is in tension with the measurements of precision electroweak observables at LEP/SLC.