The mechanical behavior of nanoparticle assemblies depends on complex particle interactions that are difficult to study experimentally. Depending on the nanoparticle morphology, these interactions could lead to adhesive and elastic−plastic behavior during contact deformation. The aim of this research is to study the effect of contact interactions between polymer nanoparticles and their impact on the macroscopic properties of formed aggregates. For this purpose, the discrete element method (DEM) was used to develop an interaction model combining elastic−plastic deformation and adhesion to study the behavior of spherical polymeric nanoparticles. Initially, a pair of particles interacting in the normal direction was simulated to evaluate the effect of adhesion and plastic deformation in the pull-off force of the contact. Based on these results, the simulations were extended to a dispersed system of nanoparticles, in which multibody interactions become dominant. Considering the aggregation between the nanoparticles induced by a shear flow, we performed an analysis of the number of aggregates and aggregates size in time to characterize the strength of clusters formed during the process. The simulation results showed that the interaction strength upon breakage of the clusters, correlating with the aggregates size, depends on the nanoparticle's softness. In this way, we verified that the type of contact interaction directly influences the macroscopic mechanical response of nanoparticle assemblies. Therefore, our model represents a new way of predicting the mechanical behavior of polymer nanoparticle systems and of optimizing it by adjusting primary particle properties.