Chemically architectured high entropy alloys are a new concept of multi-scale microstructure originally including a 3D network of composition fluctuations, named interphase. To unravel the strengthening contribution of each entity of the microstructure, chemically architectured alloys were processed, their microstructure and mechanical properties were characterized and then they were modelled by the finite element method. Nanoindentation measurements reveal a local extra-hardening at the interphase. Conventional modelling, even when considering three phases in a full-field approach, could not reproduce the compression properties, indicating again the existence of an extra-hardening. Then, the chemical and plastic strain gradients effects were included in the model and an agreement was reached with experimental data. Both experimental and modelling results prove that chemical gradients are at the origin of a new strengthening mechanism. This chemical gradient strengthening depends on the many microstructural parameters of chemically architectured alloys and opens the way for tuning and optimization of mechanical properties.