The behavior of thermoresponsive polymer poly(N-isopropylacrylamide) (PNiPAM), an essential building block in the design of smart soft materials, in aqueous solutions has attracted much interest, which contrasts with our knowledge of N-isopropylacrylamide (NiPAM) monomer. Strikingly, the physicochemical properties of aqueous NiPAM are similarly rich, and their understanding is far from being complete. This stems from the lack of accurate thermodynamic data and quantitative model for atomistic simulations. In this joint study, we have probed the thermodynamic behavior of aqueous NiPAM by experimental methods, molecular dynamics (MD) simulations, and Kirkwood-Buff (KB) analysis at ambient conditions. From the partial molar volumes and simultaneously correlated osmotic coefficients, with excess partial molar enthalpies of NiPAM in water, the concentration and temperature dependence of KB integrals was determined. For the purpose of this work, we have developed and employed a novel NiPAM force field, which not only reproduces KB integrals (G(ij)) and adequately captures macroscopic thermodynamic quantities but also provides more accurate structural insight than the original force fields. We revealed in the vicinity of NiPAM the competing effect of amide hydration with interaction between nonpolar regions. This microscopic picture is reflected in the experimentally observed NiPAM-NiPAM association, which is present from highly dilute conditions up to the solubility limit and is evidenced by G(22). From intermediate concentrations, it is accompanied by the existence of apparent dense-water regions, as indicated by positive G(11) values. The here-employed KB-based framework provided a mutually consistent thermodynamic and microscopic insight into the NiPAM solution and may be further extended for ion-specific effects. Moreover, our findings contribute to the understanding of thermodynamic grounds behind PNiPAM collapse transition.