Tuning the surface composition of metal vanadates using different cations leads to the development of a new class of highly effective catalysts tested in the ammoxidation of 2-methylpyrazine. Especially, an enrichment of V in the near-surface region is beneficial for improved selectivity. With this approach, a knowledge based optimisation of the catalysts was possible for the first time, which indeed led to highly efficient novel LaVO_x catalysts with a high yield of 2-cyanopyrazine (≥85%) and extremely high space-time-yields (ca. 525 g⁻¹_CP kg⁻¹_cat h⁻¹).