A methodological approach is presented for computing the structural formula of clay minerals from transmission electron microscopy–energy-dispersive X-ray spectroscopy (TEM-EDX) data of individual particles, including pure and complex interstratifications. The combination of TEM-EDX and modelling of XRD patterns enables the refinement of the TEM-EDX-based structural formula. This methodology allows identification of the mineral composition and mineral transformations happening in both geological and industrial processes.