This thesis introduces modern computational approaches for quantifying and analyzing both intra- and intermolecular interactions. An original formalism to quantify intramolecular interactions ab initio is first introduced. Inspired from intermolecular Symmetry-Adapted Perturbation Theory (SAPT), we derive a zeroth-order wavefunction, Ψ(0), suitable for development of an intramolecular variant of SAPT. Ψ(0) is constructed based upon the Chemical Hamiltonian concept and uses strictly localized orbitals to suppress the interactions between two intramolecular fragments. As a result, the total zeroth-order energy corresponds to a relaxed wavefunction that excludes interactions between relevant intramolecular fragments. Numerical tests on propane and halogenated derivatives yield both reasonable energy convergence and intuitive chemical trends. Moreover, the proposed scheme provides a promising description of intramolecular hydrogen bonds and energy profiles. Thus, Ψ(0) delivers the relevant information necessary to the prospected derivation of intramolecular SAPT. Besides our quest for a rigorous ab initio intramolecular energy scheme, we also propose a simpler method based on bond separation reactions to assess (de)stabilizing interactions associated with various 1,3-nonbonded substituent patterns within highly branched alkanes. While n- and singly methylated alkanes show positive bond separation energies (BSE) (i.e., stabilization), which increase systematically along the series, permethylated alkanes are characterized by decreasing BSEs (i.e., destabilizing interactions). Our quantitative analysis shows that singly methylated alkanes are more stabilized than linear alkane chains and that the unique destabilizing feature of permethylated alkanes arises from the close proximity of bulky methyl groups causing highly distorted geometries along the carbon backbone. The enhancement of intermolecular interactions constitutes yet another objective of this thesis. We demonstrate that π-depleted polyaromatic molecules present superior π-stacking ability. This somewhat counterintuitive realization is quantified using a novel computational criterion, LOLIPOP, that identifies π-conjugated frameworks presenting the desired electronic features. The screening of molecular targets benefits greatly from such a rational design criteria, which can detect the most promising candidates. The utility of the LOLIPOP criterion is thus demonstrated by identifying chemosensors presenting enhanced π-stacking ability. In particular, we have designed tailored chemosensors, which display remarkable sensitivity and selectivity towards caffeine relying upon the formation of π-π stacked complexes. Finally, the importance of weak intermolecular interactions was also shown to be essential when considering an assembly of four tetrathiafulvalene (TTF) molecules as a potential metal-free molecular catalyst for the four-electron reduction of O2 to H2O. Based on experimental evidence, we demonstrated that vii Acknowledgements the formation of a non-covalently bond helical tetramer [TTF4H2]2+ is able to deliver the needed four electrons and protons to convert O2 into water.