Abstract: Technetium-99 (⁹⁹Tc) is a pivotal indicator nuclide in radiochemical diagnostics, nuclear fuel characterization, and burn-up analysis. Its significance stems from a combination of high fission yield, long half-life and pronounced environmental mobility, establishing it as the most critically studied isotope within the technetium series. Accurately determining trace amounts of ⁹⁹Tc in the presence of the same isotopes is a challenging analytical task. Conventional mass spectrometric methods often fall short, as they are fundamentally limited by unresolvable isobaric interferences from other elements, which obscure the accurate detection of ⁹⁹Tc. To overcome this persistent limitation, laser resonance ionization mass spectrometry (LRIMS) has emerged as the preeminent analytical technique. By exploiting the element-specific, stepwise excitation and ionization of atoms via precisely tuned lasers, LRIMS achieves exceptional isotopic selectivity, effectively suppressing isobaric background. In this study, a LRIMS method for the analysis of trace technetium was established. A comprehensive and systematic investigation was undertaken to identify the optimal experimental configuration. This work involved a systematic comparative evaluation of several atomic excitation pathways to maximize the overall ionization efficiency for technetium. Furthermore, the influence of critical operational parameters was thoroughly examined. These included the precise central wavelength and optical power of each ionization laser, as well as the methodology for preparing the sample filament (the measurement source). Significant effort was also dedicated to rigorously optimizing the experimental conditions to mitigate non-resonant thermal ionization interference, thereby fully leveraging the technique’s inherent and superior advantage in overcoming isobaric interference. The results demonstrate that the four-step ionization scheme, 4d⁵5s²→4d⁶5p→4d⁶6s→autoionizing state, provides a superior ionization cross-section for technetium. The optimized laser system utilizes central wavelengths of 313.210, 821.300, and 670.491 nm for the three excitation steps, respectively. Saturation of the ionization yield is achieved at a power level of approximately 500 mW for the second-step laser. Through refinement of the filament preparation and sample deposition protocol, a measurement source containing merely 1 ng of ⁹⁹Tc is subjected to LRIMS analysis. Through the adoption of the electroplating preparation process, mass spectrometric analysis of a 1 ng ⁹⁹Tc measurement source reveals a peak signal intensity reaching approximately 40 000 s⁻¹. The overall detection efficiency is quantified to be on the order of 10⁻⁶, while the elemental selectivity against potential interfering species exceeds 8×10⁶. This work conclusively establishes a highly sensitive and selective LRIMS-based methodology, providing a robust and feasible solution for the precise determination of ultratrace ⁹⁹Tc in challenging nuclear and environmental samples.