Two-dimensional (2D) Janus WSSe has attracted considerable attention for optoelectronic device applications due to its unique structural asymmetry and exceptional electronic and optical properties. However, intrinsic defects inevitably introduced during experimental growth can significantly modulate its material properties and device performance. In this work, first-principles calculations were performed to systematically investigate the impacts of vacancies, interstitials, and antisite defects on the geometric structure and electronic properties of Janus WSSe monolayer. Furthermore, the roles of sulfur vacancies (VS) and selenium vacancies (VSe) in modulating the electronic and optical properties of the 2D ZnO/WSSe van der Waals heterostructure are explored. In the isolated two-dimensional 2H-WSSe monolayer, although VS and VSe defects are identified as deep-level defects, the calculated carrier capture coefficients and capture cross sections reveal that they do not act as effective nonradiative recombination centers. Regarding the ZnO/WSSe heterostructure, the introduction of VS and VSe narrows the bandgap, enhances low-energy light absorption, and modulates interfacial charge transfer without disrupting the heterostructure stability. This work provides a solid theoretical foundation for defect engineering in WSSe-based materials and the design of high-performance ZnO/WSSe heterostructure optoelectronic devices.