Background Nanopore adaptive sampling (NAS) offers a promising approach for assessing genetic diversity in targeted genomic regions. Here we designed and validated an experiment to enrich a set of resistance genes in several melon cultivars as a proof of concept.Results We showed that, using a single reference, each of the 15 regions we identified in two newly assembled melon genomes (ssp. melo) was also successfully and accurately reconstructed in a third ssp. agrestis cultivar. We obtained fourfold enrichment regardless of the tested samples, but with some variations according to the enriched regions. The accuracy of our assembly was further confirmed by PCR in the agrestis cultivar. We discussed parameters that could influence the enrichment and accuracy of NAS generated assemblies.Conclusions Overall, we demonstrated that NAS is a simple and efficient approach for exploring complex genomic regions. This approach facilitates resistance gene characterization in a large number of individuals, as required when breeding new cultivars suitable for the agroecological transition.