As high brittleness limits the application of all epoxy resins (EP), here, it can be modified by high-performance thermoplastic poly(ether nitrile ketone) containing phthalazinone structures (PPENK). Therefore, the influence of different PPENK contents on the mechanical, thermal, and low-temperature properties of EP was comprehensively investigated in this paper. The binary blend of PPENK/EP exhibited excellent properties due to homogeneous mixing and good interaction. The presence of PPENK significantly improved the mechanical properties of EP, showing 131.0%, 14.2%, and 10.0% increases in impact, tensile, and flexural strength, respectively. Morphological studies revealed that the crack deflection and bridging in PPENK were the main toughening mechanism in the blend systems. In addition, the PPENK/EP blends showed excellent thermal and low-temperature properties (−183 °C). The glass transition temperatures of the PPENK/EP blends were enhanced by approximately 50 °C. The 15 phr of the PPENK/EP blends had a low-temperature flexural strength of up to 230 MPa, which was 46.5% higher than EP. Furthermore, all blends exhibited better thermal stability.