Improving potato late blight (LB) resistance is essential for ensuring food security, particularly using wild relatives endemic to Phytophthora infestans – prone regions. However, reproductive barriers can impede the transfer from potato wild relatives (PWR) to the cultivated genepool. This study sought to incorporate potentially novel LB resistance from wild diploid accessions of Series Piurana (S. chiquidenum, S. paucissectum, and S. piurae), Tuberosa (S. cajamarquense), and Megistracroloba (S. sogarandinum) into tetraploid potato. Trough rescue pollination, 699 diploid interspecific hybrids were obtained, of which 385 displayed LB resistance in two endemic environments. Based on a comprehensive evaluation, including assessing 2n pollen production, 14 diploid interspecific hybrids were selected to continue the introgression process. These pre-bred stocks were then used in interploidy (4x-2x) crosses to incorporate their LB resistance in the cultivated tetraploid background. Assessment of 1978 genotypes resulting from interploidy crosses under endemic disease pressure yielded 717 hybrids with moderate to high levels of LB resistance. Evaluation of pollen viability and ploidy revealed moderate fertility and predominantly tetraploid genotypes. Reassessment of LB resistance on this new subset of hybrids further identified 214 genotypes with sustained resistance. Among them, 12 tetraploid hybrids with low glycoalkaloid content, favorable agronomic and post-harvest attributes were identified as crossing-friendly stocks. Notably, 11 of these hybrids were derived from S. cajamarquense and one from S. sogarandinum. These promising 4x hybrids are now primed to be incorporated into potato breeding programs.