Due to their (semi)flexible backbones and varied composition, polymers explore astronomically larger and more complex configurational spaces than small “rigid” molecules. For example, a single 2d lattice polymer chain composed of only 15 segments can access O(10^8) conformations, whereas a rigid molecule possesses a single conformer. Consequently, entropy becomes increasingly important in describing the equilibrium behavior of polymers with high molecular weights or complex architectures. Despite its key role, entropy is often overlooked in materials design due to its nuanced, hard-to-quantify nature, and non-trivial coupling to enthalpic interactions. In this dissertation, we show that entropy can not only be a key driver of spontaneous processes but also engender rather unexpected but sought-after behaviors in polymeric systems. In the first example, we develop a coarse-grained molecular dynamics model to study the cooperative adsorption (i.e., bulk concentration dependent adsorption affinity) of polymer chains on nanoparticles (NP) of different structures. By exploring a large parameter space for polymer-polymer (mediated by solvent effect) and polymer-NP interactions, we found that, consistent with experiments, the strength of cooperativity is related to solvent quality and relative interaction strengths between the polymer and the adsorbent. We also found that cooperativity is entropically enhanced for longer chains: confinement to NP facets for positive cooperativity, and loss of conformational entropy of associating chains for negative cooperativity. In the second example, we develop and apply multiscale molecular modeling and a semi-empirical framework for unveiling design rules for the effective binding of sequence-defined oligomers, using oligocarbamates (SeDOCs) as testbed. This work emphasizes the role of intramolecular bonding in designing robust intermolecular binding of SeDOCs through entropically favorable binding-induced conformational changes. Predesigned binding-induced conformational changes can be exploited for the deployment of molecules for uses in, e.g., on-demand catalysis and assembly of oligomer-grafted nanoparticle mixtures into complex morphologies. In the third example, we propose a mechanistic model to explain the experimentally observed anomalous extension behavior of model polymer bottlebrushes (i.e., zero- and negative-scaling of chain extension with applied force) using multiscale molecular simulations and theory. We first identify two key sources of cis-trans isomerism: brush isomers (defined by the orientation of neighboring brushes) and backbone isomers (defined by the dihedral angle around the double bond). We show that brushes isomerization manifests into a zero-scaling extension in the intermediate force regime. Furthermore, we show that negative scaling is plausible under force-induced backbone isomerization. We also illustrate that these anomalous behaviors reflect deviations of the polymer’s conformational entropy from classical models of polymer elasticity. These features enable the use of bottlebrushes as shock absorbers and smart adhesives that undergo, akin to phase changing materials, structural changes to become stiffer under external forces. In summary, these examples illustrate the importance of engineering entropy to achieve enhanced material properties, especially in polymeric systems.