Abstract: High-purity nickel targets, as critical materials in semiconductor and integrated circuit industries, require stringent purity control and verification. Glow Discharge Mass Spectrometry (GD-MS), serving as a high-sensitivity compositional analysis technique, represents the primary method for purity assessment of high-purity metals. However, its quantitative analysis necessitates matrix-matched certified reference materials (CRMs) to calibrate relative sensitivity factors (RSFs) of elements. Presently, the scarcity of CRMs for high-purity nickel analysis and the limitations of conventional high-temperature fusion methods in achieving multi-element doping pose significant challenges. This study developed a novel methodology for fabricating metallic matrix reference materials through powder metallurgy technology, with systematic investigations on doping strategies, compaction pressure, sintering atmosphere, and temperature. Results demonstrate that both drop-coating and immersion methods effectively incorporate trace elements into carbonyl nickel powders. Comparatively, drop-coating exhibits superior suitability for large-scale production due to minimized elemental loss and reduced oxidation during doping. In powder metallurgy processing, excessive compaction pressure induces sample cracking that compromises densification enhancement, while overly high temperatures and reductive atmospheres provoke substantial elemental loss. Insufficient sintering temperatures hinder internal stress relief, limiting densification improvement through repressing. Optimal parameters (700 MPa compaction pressure, 700°C sintering temperature, and inert atmosphere) achieved 89% density while effectively preserving doped elements. Additionally, the feasibility of 3D printing for reference material preparation was explored. The 3D-printed samples exhibited higher densification than powder-metallurgy counterparts with retained impurity elements, demonstrating promising potential for CRM fabrication. This work provides technical insights into standardized preparation methods for high-purity nickel matrix reference materials.