A thermally-activated constitutive model is developed based on dislocation interactions, crystallographic orientations and microstructural evolution to describe the elasto-plastic stress–strain behavior during multi-axial loading. The aim is to contribute to the quantification of complex strain path response in solid solution strengthened alloys. In detail, dislocation/dislocation interactions are incorporated in the model to quantify latent and kinematic hardening phenomena during loading path changes. Dislocation density-based constitutive relations are included to account for dislocation features such as dislocation forests, walls and channels. Moreover, dislocation/solute atom interactions are also considered in order to account for both dynamic and static strain aging as well as static recovery. The model is validated against multiple multi-axial data sets for AA5754-O with changes of loading path and various degrees of pre-strain and time intervals between tests.