Watermelon (Citrullus lanatus) and melon (Cucumis melo) are globally important cucurbit crops, with China being the largest producer and consumer. Traditional breeding methods face difficulties in significantly improving yield and quality. Smart breeding, which combines genomics, gene editing, and artificial intelligence (AI), holds great promise but fundamentally depends on understanding the molecular mechanisms controlling important agronomic traits. This review summarizes the progress made over recent decades in discovering and understanding the functions of genes that control essential traits in watermelon and melon, focusing on plant architecture, fruit quality, and disease resistance. However, major challenges remain: relatively few genes have been fully validated, the complex gene networks are not fully unraveled, and technical hurdles like low genetic transformation efficiency and difficulties in large-scale trait phenotyping limit progress. To overcome these and enable the development of superior new varieties, future research priorities should focus on the following: (1) systematic discovery of genes using comprehensive genome collections (pan-genomes) and multi-level data analysis (multi-omics); (2) deepening the study of gene functions and interactions using advanced gene editing and epigenetics; (3) faster integration of molecular knowledge into smart breeding systems; (4) solving the problems of genetic transformation and enabling efficient large-scale trait and genetic data collection (high-throughput phenotyping and genotyping).

Watermelon is an economically important horticultural crop cultivated worldwide. The ERF family is one of the largest transcription factor families in plan