The effectiveness of e-nose systems as high-throughput tools for volatile profiling in watermelon was investigated focusing on discerning subtle changes induced by the use of different rootstocks. Partial Least Square Discriminant Analysis (PLS-DA) models, both GC-MS and e-nose data, demonstrated moderate performance in classification due to nuanced differences among groups (the same F1 hybrid was used as scion). However, PLS-DA biplots revealed a clear correlation between GC-MS and e-nose data. This methodology enabled the e-nose system to identify the effects of specific root-scion combinations compared to non-grafted controls and detect combinations with more variable volatile profiles. Remarkably, the e-nose system identified samples with anomalous volatile profiles, mirroring the capabilities of GC-MS data. Additionally, PLS models were developed to provide reasonably accurate predictions of key compound contents like geranylacetone, (Z)-6-nonen-1-ol, or (Z)-6-nonenal, crucial for watermelon flavor and taste perception. Overall, this study highlights the potential of e-nose systems in discerning nuanced variations in watermelon volatile profiles affecting aroma. Incorporating volatile profile evaluation capabilities using such systems will significantly optimize quality control processes and plant breeding programs.