Our strategy to address this problem relies on the well-established Local Energy Decomposition (LED) scheme at the domain-based local pair natural orbital cluster level incorporating singles, doubles, and perturbative triples, i.e., DLPNO-CCSD(T). For a complex system with an arbitrary number of fragments, the LED scheme allows the exact decomposition of the electronic energy into additive terms, corresponding to the fragment energies (also called -intra-fragment‖ terms) and their pairwise interactions. The latter can also be decomposed into contributions from fragment-pairwise electrostatics, exchange and London dispersion (LD), thus providing additional physical insight. This approach has proven to be instrumental in both the strong-and weak-interaction regimes for closed-and open-shell systems, and thus finds widespread application. LED also provides a simple definition for cooperativity effects and many-body terms. A primary application area for the LED scheme lies in dissecting binding energies between two or more complex chemical entities, each one potentially constituting of many fragments, into contributions from individual fragment-pairwise interactions. This is highly relevant in fields such as supramolecular chemistry, catalysis, materials science and drug discovery. For instance, the LED scheme can provide insights into the contribution of individual ligand-residue interactions to the binding energy of a ligand to a protein receptor. Unfortunately, a major limitation of the LED scheme when more than two fragments are considered (alongside other schemes that have similar features) is that it cannot be used to quantify the net effect on the binding energy of two chemical entities (e.g., a protein and a ligand) stemming from the interaction between two fragments (e.g., a residue in the active site of the protein and a functional group in the ligand). This net fragmentpairwise interaction energy has contributions from intra-as well as inter-fragment energy terms. The intra-fragment terms contribute because the electronic and geometric structure of the individual fragments is perturbed upon binding, while the inter-fragment terms represent genuine interaction energy contributions such as electrostatics, exchange and LD. However, if there are more than two fragments, the intra-fragment terms contain contributions from all other fragments and this prevents a breakdown of the interaction energy into clear pairwise contributions. For example, each intrafragment term is influenced by polarization effects originating from the short-range repulsive contributions resulting from its interaction with the remaining N-1 fragments. Hence, what would be desirable is to have a scheme where the binding energy between two complex chemical systems is exactly expressed into fragment-pairwise interaction energy terms. This is what will be developed below. This method will enable us to ascertain whether interactions between molecular fragment pairs in any chemical system are overall attractive or repulsive, and to precisely measure their strength at the coupled cluster level. This would significantly improve our capacity to predict molecular behavior and properties, facilitating advancements across various fields of chemical research. Specifically, we introduce herein an extension of the LED methodology to accurately quantify fragment-pairwise interaction energy contributions to the binding energy between complex chemical entities at the gold standard CCSD(T) level. This purely -fragment-pairwise‖ LED (fp-LED) scheme requires only a single supramolecular DLPNO-CCSD(T) binding energy calculation. We illustrate this method with examples from various fields of chemical research, addressing a range of representative problems: