Nucleopalladation is one of the most common mechanisms for Pd-catalyzed hydro- and oxidative functionalization of alkenes. Due to the electronic bias of the pi-alkene-palladium complexes, nucleopalladations with terminal aliphatic alkenes typically deliver the nucleophile to the more substituted sp(2) carbon to form the Markovnikov-selective products. The selective formation of the anti-Markovnikov nucleopalladation products requires the inherent electronic effects to be overridden, which is still a significant challenge for reactions with simple aliphatic alkenes. Because the interactions between the nucleophile and the alkene substrate are influenced by a complex combination of multiple types of steric and electronic effects, a thorough understanding of the interplay of these underlying interactions is needed to rationalize and predict the regioselectivity. Here, we employ an energy decomposition approach to quantitatively separate the different types of nucleophile-substrate interactions, including steric, electrostatic, orbital interactions, and dispersion effects, and to predict the impacts of each factor on regioselectivity. We demonstrate the use of this approach on the origins of catalyst-controlled anti-Markovnikov-selectivity in Hull's Pd-catalyzed oxidative amination reactions. In addition, we evaluated the regioselectivity in a series of nucleopalladation reactions with different neutral and anionic Pd catalysts and N- and O-nucleophiles with different steric and electronic properties. On the basis of these computational analyses, a generalized scheme is established to identify the dominant nucleophile-substrate interaction affecting the regioselectivity of nucleopalladations with different Pd catalysts and nucleophiles.