Decapsulation is a failure analysis technique often used to expose the die and first-level interconnects such as wirebonds by dissolving the surrounding epoxy molding compound (EMC). The wet decapsulation technique, which uses fuming acids, works very well for traditional gold (Au) wirebonds. On the other hand, its latest alternative, copper (Cu) wirebond, reacts with the nitric acid vigorously and undergoes severe corrosion. It is important to develop an acid chemistry that can be used to perform decapsulation of Cu–Al incorporated plastic encapsulated microelectronics (PEMs) without damaging the Cu wires. This paper presents the wet decapsulation technique based on different ratios of the red fuming nitric acid and concentrated sulfuric acid. Quality of post-decap part was examined using reduction in the wire diameter and changes in ball shear strength. Reduction in wire diameter was monitored with the scanning electron microscopy (SEM), and shear strength was measured using a DAGE2400 shear tester. These tests were performed on the PEMs molded with different EMCs, wire diameters, and pad thickness to cover process as well as geometric variability. Artificial neural network with Bayesian regularization-based model has been developed correlating the decapsulation process parameters with the post-decap wire diameter reduction and shear strength of the wirebond. Stepwise regression was used to identify the significant variables that affect the decap process. The influential variables were then used to develop a predictive model for prediction of the percent reduction in wire diameter and change in shear strength separately. Models were then validated with the test data set.