Quality is a key aspect in the era of Industry 4.0. Zero-defect manufacturing (ZDM) as the latest quality assurance approach. It can be implemented in two different approaches: the product-oriented and the process-oriented ZDM. It is important to know how and when to consider adopting one approach over the other. To achieve that there is the need for analyzing the differences of the two ZDM approaches. However, the current literature lacks a detailed analysis and comparison of these two approaches to ZDM implementation. Earlier studies on the topic have adopted one of these approaches over the other without evaluating how it fits with specific cases. The literature of the last decade indicates a movement towards product-oriented approaches, but it has not shown proof why product oriented was used over process oriented. Guided by these gaps, this research work creates a model for quantifying the effects of the implementation of both the product-oriented and process-oriented ZDM approaches. The proposed model considers all the critical parameters that affect the problem and serves as an assisting tool to engineers during the design or re-configure manufacturing systems, for choosing the most efficient ZDM approach for their specific cases. The robustness of the model was analyzed using the design of experiments method. The results from both the designed experiments and an industrial use case illustrate that in most cases, product-oriented ZDM performs better than the process-oriented approach. Nevertheless, in our analysis, we also highlight strong interactions between some factors that make the selection between product-oriented and process-oriented ZDM difficult and complex.