Sequential infiltration synthesis (SIS) is a scalable and valuable technique for the synthesis of organic–inorganic materials with several potential applications at the industrial level. Despite the increasing interest for this technique, a clear picture of the fundamental physicochemical phenomena governing the SIS process is still missing. In this work, infiltration of Al 2 O 3 into thin poly(methyl methacrylate) (PMMA) films using trimethyl aluminum (TMA) and H 2 O as precursors is investigated by operando dynamic spectroscopic ellipsometry (SE) analysis. The TMA diffusion coefficient values at temperatures ranging from 70 to 100 °C are determined, and the activation energy for the TMA diffusion process in PMMA is found to be E a = 2.51 ± 0.03 eV. Additionally, systematic data about reactivity of TMA molecules with the PMMA matrix as a function of temperature are obtained. These results provide important information, paving the way to the development of a comprehensive theory for the modeling of the SIS process.