Abstract: To enhance the performance of Class 1E Category K3 instrumentation cables for nuclear power plants, an integrated anti-interference long-life cable structure was proposed. In the developed cable, a composite shielding layer wound with high-permeability alloy wires and aramid fibers was employed, providing both electromagnetic shielding and mechanical protection functions. A co-extruded layered gradient design was adopted for the insulation and sheath to improve environmental resistance. Meanwhile, an embedded optical fiber sensing unit enables distributed real-time monitoring of temperature and vibration along the entire cable length. Finally, the reliability and feasibility of the cable structure were verified through intelligent detection function verification, electromagnetic compatibility tests, mechanical performance tests, insulation thermal aging life prediction, long-term durability tests of the sheath, and long-term reliability tests of the integrated optical fiber sensing unit. Results showed that temperature measurement error of integrated optical fiber sensing unit was kept within ±1.5 °C, and vibration localization accuracy of ±1 m was achieved, shielding effectiveness of 26.4 dB was reached at 50 Hz power frequency, tensile load-bearing capacity of over 2 200 N was obtained, predicted service life lower limit of 68 years for the insulation system at 90 °C was calculated; and the validated service lives of both the sheath and the optical fiber unit after accelerated thermal aging were proved to meet the requirement of at least 60 years. In conclusion, the electromagnetic compatibility, mechanical strength, durability, and intelligence of the cable were significantly enhanced by the proposed design, making it suitable for high-reliability instrumentation and control circuits in nuclear power plants.