Deep-space exploration expands from lunar and Mars missions to Jupiter, Saturn and beyond the outer solar system, even interstellar exploration. As distance from the Sun increases, solar panel power output declines quadratically. Beyond Jupiter’s orbit, solar power cannot support probe operation, making space nuclear power the only sustainable energy solution. Space nuclear power systems include Radioisotope Thermoelectric Generators (RTG), space nuclear reactors and radioisotope heat power units, providing low‑voltage DC output of several tens of volts. However, electric propulsion, scientific payloads and communication subsystems require high‑voltage DC from hundreds to thousands of volts. As the core power conversion module, the high‑voltage conversion unit steps up low nuclear power voltage to stable high voltage. Its efficiency, in‑orbit reliability and long‑life performance directly determine energy utilization, mission endurance and exploration objectives. Deep‑space nuclear power imposes extreme challenges far beyond LEO applications: 1.Ultra‑high efficiency requirement: RTG thermoelectric efficiency is merely 6%–8%, and reactor power is constrained by volume and mass. Every 1% efficiency gain increases available power for payloads and propulsion, extending mission life. Full‑load efficiency ≥95% and peak efficiency ≥97% are mandatory. 2.Extreme long lifespan and reliability: Missions last decades with 10–30 years of maintenance‑free continuous operation under intense radiation, high vacuum and extreme temperature cycling; any single failure may abort the entire mission. 3.High step‑up ratio conflict: Nuclear power outputs 28 V–48 V low voltage, while high‑voltage demand reaches 1,000 V–3,000 V with boost ratios exceeding 100:1; conventional single‑stage converters cannot balance high gain and high efficiency. The design complies with GJB 3758‑99, GB/T 42037‑2022 and NASA‑STD‑7009, meeting long‑life, high‑reliability and maintenance‑free requirements for deep‑space nuclear power. This methodology establishes a full‑process framework covering high‑efficiency topology, full‑chain loss optimization, high‑ratio energy conversion, ultra‑long‑life reliability and deep‑space environmental adaptation, applicable to RTG and reactor high‑voltage conversion and supporting domestic nuclear power localization. Adopting three‑stage cascaded resonant topology + fully digital adaptive control + full‑range soft switching, combined with wide‑bandgap semiconductors and integrated magnetics, it breaks traditional efficiency limitations under extreme boost ratios, achieving peak efficiency and over 30 years of in‑orbit service. Five core design principles are defined: 1.Three‑stage cascaded resonant architecture divides voltage elevation into low‑current pre‑regulation, isolated secondary boosting and precision high‑voltage output. Stage 1: multi‑phase interleaved synchronous boost raises 28 V–48 V to a stable 400 V intermediate bus with ≥99% efficiency and minimized input ripple. Stage 2: full‑bridge LLC resonant isolation achieves galvanic separation and secondary boosting to approximately 1,000 V with full ZVS/ZCS soft switching and ≥98% efficiency. Stage 3: symmetric voltage multiplication delivers final 1,000 V–3,000 V high voltage with precise regulation and low ripple. Each stage limits gain within 10×, avoiding excessive transformer leakage inductance and efficiency degradation. 2.Full‑chain soft switching eliminates hard‑switching losses across all stages. Critical conduction mode ensures ZVS turn‑on and ZCS turn‑off for the front stage; optimized LLC resonance maintains soft switching from 10% to 100% load; low‑loss post regulation minimizes residual dissipation, reducing overall switching losses by over 90%. 3.Full wide‑bandgap adoption applies GaN HEMTs for low‑voltage high‑current stages to cut conduction and switching losses; SiC MOSFETs and SiC Schottky diodes dominate high‑voltage sections, reducing high‑power losses by over 70% with superior radiation tolerance and high‑temperature stability for multi‑decade missions. 4.Integrated magnetic design combines boost inductors, resonant inductors and transformers onto shared magnetic cores, reducing size by ≥40% and mass by ≥35%. Planar matrix transformers achieve leakage inductance ≤2 μH and coupling coefficient ≥0.998, minimizing high‑frequency winding losses. 5.Fully digital adaptive efficiency control uses radiation‑hardened DSP+FPGA to dynamically tune frequency, dead time, phase and duty cycle in real time, maintaining optimal efficiency under all operating conditions while enabling closed‑loop regulation, in‑orbit calibration and full fault protection. Full‑chain loss optimization maximizes efficiency across five dimensions: Topology optimization eliminates diode conduction loss via synchronous rectification and reduces voltage stress through symmetric voltage doubling. Component optimization selects ultra‑low‑loss GaN/SiC devices, low‑ESR film capacitors and low core‑loss nanocrystalline magnetic materials to minimize inherent dissipation. Magnetic optimization reduces core and winding losses via integrated magnetics, interleaved Litz‑wire windings and active snubber energy recovery. Control optimization implements dynamic dead‑time tuning, frequency optimization, burst‑mode light‑load operation and adaptive multi‑phase interleaving to guarantee ≥95% efficiency across all loads. Thermal optimization adopts full conduction cooling with high‑thermal‑conductivity substrates connected to deep‑space radiators; uniform component layout restricts temperature deviation ≤10 ℃; thick copper PCBs lower conductive loss and enhance heat spreading. Deep‑space environmental adaptation and ultra‑long‑life reliability ensure 30+ years of radiation, vacuum and extreme temperature resilience: Three‑level radiation hardening selects high‑total‑dose devices (≥200 krad(Si)) and high LET tolerance (≥80 MeV·cm²/mg); triple modular redundancy and EDAC protect control logic; reinforced shielding mitigates high‑energy particle damage. Ultra‑long‑life over‑derating applies strict aerospace Level‑I derating at 80% margin with no electrolytic capacitors or moving parts; dual hot redundancy prevents single‑point failure; lifetime monitoring dynamically adjusts operating stress to slow aging. Extreme environmental compatibility ensures stable performance from −55 ℃ to +125 ℃; vacuum potting and nitrogen sealing prevent corona discharge; high‑emissivity thermal coatings enhance deep‑space radiation cooling. Autonomous in‑orbit monitoring integrates full‑parameter telemetry, intelligent fault diagnosis, redundant switching and self‑recovery for long‑term unattended deep‑space operation. In summary, this integrated framework resolves traditional conflicts between ultra‑high boost ratios and extreme efficiency while achieving 30+ years of maintenance‑free deep‑space reliability. The three‑stage soft‑switch cascaded design delivers peak efficiency ≥97% and full‑load efficiency ≥95%; comprehensive radiation hardening and over‑derating guarantee multi‑decade service. It fully supports high‑voltage conversion for all deep‑space nuclear power systems and provides core domestic technical foundations for future outer solar system and interstellar exploration.