The impact of Emtricitabine (EMTB) on the treatment of human immunodeficiency virus (HIV) infection is influenced by its active molecular structure. This study investigates into the interaction of EMTB in aqueous systems at various temperatures. Physicochemical properties (PCPs) such as density (ρ, g cm-3), Apparent Molar Volume (Vϕ, cm3•mol−1), viscosity (η, mPa.s), and surface tension (γ, mNm-1) of EMTB in aqueous solutions have been measured at temperatures of 298.15, 303.15, 308.15, and 313.15 K. These PCPs elucidate the intermolecular forces (IMF) between EMTB and water (W), with EMTB concentrations ranging from 0.02 to 0.10 millimolar (mM) in a binary system at predetermined temperatures. This investigation of PCPs to understand the molecular interaction mechanism, focusing on the nature of IMF arising during the interaction of EMTB with W at various temperatures, thereby revealing the structural dynamics of EMTB in aqueous solutions. Analysis of PCPs data reveals the interaction and structure-disrupting tendencies of EMTB with water, exhibiting a net increase as temperature decreases, indicating thermal stability. Furthermore, the PCPs data indicate occurrence of hydrogen bond (HB) and electrostatic interactions (EI) between EMTB and water, with temperature-dependent interaction activities increasing as EMTB concentration increases in the aqueous medium.