Grain refinement and precipitation are conventionally employed to enhance the mechanical properties of magnesium alloys. However, there remains a challenge in obtaining a fine grain structure together with a high-density precipitates, particularly in rare-earth containing magnesium alloys. In this study, a strong and ductile Mg-RE (WE43) alloy featuring a fine twin structure and dense nano-precipitates was fabricated via a processing combining multi-directional compression with multi-intermediate aging. The mechanical characterization demonstrated that the fabricated WE43 alloy exhibits an exceptional work-hardening capacity and enhanced ultimate tensile strength, albeit with some compromise in yield strength. Microstructural investigations reveal that the multi-directional compression promotes extensive grain refinement through the formation of nanostructured deformation twins, while the multi-intermediate aging inhibits twin expansion via solutes and precipitates pinning along twin boundaries. Further transmission electron microscopy analysis revealed the formation of high-density nano-precipitates within the matrix. The fine twins and dense precipitation structure strongly promote dislocation multiplication and accumulation, by interaction among dislocations, twin boundaries and nano-precipitates, leading to the significantly improved work-hardening capability and ultimate strength. The current study presents a new approach for the fabrication of rare-earth containing magnesium alloys with high ductility and ultimate strength.