This study presents a method to generate clonal gametes in hybrid tomato plants through a 'mitosis instead of meiosis' (MiMe) system, enabling the engineering of polyploid genomes. By mutating key genes involved in meiosis (SlSPO11-1, SlREC8, and SlTAM), researchers successfully produced clonal, unreduced gametes in three hybrid tomato genotypes. These gametes were used to create '4-haplotype' (4-Hap) plants, which contain the complete genetic repertoire of their four inbred grandparents. The 4-Hap plants exhibit genome-wide heterozygosity and maintain the traits of their parents, demonstrating the potential for precise polyploid genome engineering. The MiMe system allows for the controlled combination of four predefined genome haplotypes through the hybridization of clonal gametes from two distinct hybrid parents. This approach enables the generation of tetraploid plants with four distinct haplotypes, which can be used to exploit autopolyploid progressive heterosis (APH) in crops. The study shows that these 4-Hap plants have normal vegetative growth, produce well-organized inflorescences with seedless fruits, and exhibit higher chlorophyll content in mature leaves. The research highlights the potential of polyploid genome design to control genetic heterozygosity in polyploids, thereby allowing the full exploitation of APH in agriculture. This method could facilitate the introgression of one or multiple complete 'wild' genomes into cultivated crops, enhancing resistance to abiotic and biotic stresses. The study also suggests that polyploid genome design could be used to transfer genomes from diploid wild materials into current polyploid crops and generate highly heterozygous seedless triploid varieties. The findings demonstrate that clonal gamete production in hybrid crops allows precise polyploid genome engineering, which could lead to new breeding schemes and increased genetic diversity in crops. The study provides a blueprint for the controlled increase of genetic diversity in crops and opens up completely novel breeding schemes. The research has significant implications for hybrid potato breeding and other crops, offering new possibilities for genetic improvement and stress resistance.This study presents a method to generate clonal gametes in hybrid tomato plants through a 'mitosis instead of meiosis' (MiMe) system, enabling the engineering of polyploid genomes. By mutating key genes involved in meiosis (SlSPO11-1, SlREC8, and SlTAM), researchers successfully produced clonal, unreduced gametes in three hybrid tomato genotypes. These gametes were used to create '4-haplotype' (4-Hap) plants, which contain the complete genetic repertoire of their four inbred grandparents. The 4-Hap plants exhibit genome-wide heterozygosity and maintain the traits of their parents, demonstrating the potential for precise polyploid genome engineering. The MiMe system allows for the controlled combination of four predefined genome haplotypes through the hybridization of clonal gametes from two distinct hybrid parents. This approach enables the generation of tetraploid plants with four distinct haplotypes, which can be used to exploit autopolyploid progressive heterosis (APH) in crops. The study shows that these 4-Hap plants have normal vegetative growth, produce well-organized inflorescences with seedless fruits, and exhibit higher chlorophyll content in mature leaves. The research highlights the potential of polyploid genome design to control genetic heterozygosity in polyploids, thereby allowing the full exploitation of APH in agriculture. This method could facilitate the introgression of one or multiple complete 'wild' genomes into cultivated crops, enhancing resistance to abiotic and biotic stresses. The study also suggests that polyploid genome design could be used to transfer genomes from diploid wild materials into current polyploid crops and generate highly heterozygous seedless triploid varieties. The findings demonstrate that clonal gamete production in hybrid crops allows precise polyploid genome engineering, which could lead to new breeding schemes and increased genetic diversity in crops. The study provides a blueprint for the controlled increase of genetic diversity in crops and opens up completely novel breeding schemes. The research has significant implications for hybrid potato breeding and other crops, offering new possibilities for genetic improvement and stress resistance.