Interdiffusion across the interface of poly(methyl methacrylate)/poly(vinylidene fluoride) (PMMA/PVDF) was investigated thoroughly by scanning transmission electron microscopy (STEM) plus electron energy-loss spectroscopy (EELS) and energy-dispersive X-ray spectrometry (EDX) and further with the assistance of laser-Raman spectroscopy. The factors of the annealing temperature and the time on the interfacial widths and the concentration profiles of PMMA and PVDF across the interface of PMMA/PVDF have been considered in detail. It was found that the concentration profiles of PMMA and PVDF were determined by the crystallization of PVDF, especially at the high annealing temperature (220 °C) in the PMMA part of the interface. Under the influence of the PVDF crystallization, the concentration profiles of F (from PVDF) and O (from PMMA) monitored by STEM-EDX/EELS changed gradually from parabola-shape to linear-shape in the PMMA part. The activation energy for the interdiffusion across the interface of PMMA/PVDF was calculated to be 51.0 kJ/mol, lower than the other reported pairs like poly(vinyl chloride)/poly(ε-caprolactone) (PVC/PCL) (69.8 kJ/mol) and poly(styrene-ran-acrylonitrile)/poly(methyl methacrylate) (SAN-29/PMMA) (175 ± 15 kJ/mol).