Palladium-103 (¹⁰³Pd) is an Auger electron–emitting radionuclide with favorable radiophysical properties for highly localized energy deposition, making it a promising candidate for targeted radionuclide therapy. However, its broader application has been limited by challenges related to production, radiochemical separation, and in vivo validation. This study aimed to develop a complete and integrated workflow for the cyclotron production, separation, recovery, purification, radiolabeling, and preclinical evaluation of ¹⁰³Pd as a theranostic radionuclide. ¹⁰³Pd was produced via the ¹⁰³Rh(p,n)¹⁰³Pd nuclear reaction using optimized irradiation conditions. A diffusion-driven dry-distillation approach was developed for radionuclide separation, exploiting the differences in vapor pressure and diffusion behavior between palladium and rhodium at elevated temperatures. A dedicated radionuclide separation equipment (RSE) enabled selective volatilization and recovery of ¹⁰³Pd under high-vacuum conditions, providing an efficient alternative to conventional wet-chemical methods. Recovery and purification were achieved using an optimized acid-based extraction and anion-exchange chromatography. Experimental studies on palladium diffusion in rhodium supported the separation mechanism, while ICP-MS measurements demonstrated that thermal pre-treatment of rhodium foils significantly reduced residual palladium content, leading to improved specific activity of the produced radionuclide. The optimized RSE achieved separation efficiencies of 64–86% and recovery yields of 81–94%, with high chemical purity confirmed by surface analysis. Radiolabeling of ¹⁰³Pd with clinically relevant chelators (NOTA and DOTA-TATE) resulted in radiochemical purity exceeding 95%. The release of the daughter radionuclide ¹⁰³ᵐRh from [¹⁰³Pd]Pd–DOTA-TOC complexes was experimentally evaluated, with measured release fractions of 10.5 ± 2.7% and 12.0 ± 0.5%, indicating limited daughter release and favorable retention within the complex. Preclinical evaluation using SPECT/CT imaging in murine models demonstrated stable biodistribution and in vivo stability of [¹⁰³Pd]Pd-labeled constructs. Furthermore, a preliminary translational study in a spontaneous canine tumor model showed tumor localization and early indications of therapeutic response. Overall, this work establishes an integrated production-to-preclinical evaluation pipeline for ¹⁰³Pd and demonstrates its feasibility as a theranostic Auger electron–emitting radionuclide, highlighting its potential for highly localized targeted radionuclide therapy.