The article discusses the development and application of an ORFeome-based RNAi library for improving phenome mapping in *Caenorhabditis elegans*. The authors highlight the limitations of existing RNAi resources, such as their lack of flexibility and the inability to utilize the latest improvements in RNAi technology. They demonstrate that the C. elegans ORFeome resource, generated using the Gateway cloning system, can be used to create alternative HT-RNAi resources with enhanced flexibility. This approach allows for gene knockdowns under various conditions, increasing the possibilities for phenome mapping. The ORFeome-RNAi v1.1 library contains 11,511 RNAi clones targeting 10,953 unique protein-encoding genes, representing an increase of ~9% in the total number of genes that can be targeted by RNAi-by-feeding. The authors performed a genome-wide RNAi screen in WT C. elegans hermaphrodites using this library and observed phenotypes for ~10% of the genes studied. They also discuss the reproducibility of the RNAi results and the factors affecting the frequency of phenotypes. The article concludes by emphasizing the value of an ORFeome-based approach for generating alternative HT-RNAi resources and improving phenome mapping in C. elegans.The article discusses the development and application of an ORFeome-based RNAi library for improving phenome mapping in *Caenorhabditis elegans*. The authors highlight the limitations of existing RNAi resources, such as their lack of flexibility and the inability to utilize the latest improvements in RNAi technology. They demonstrate that the C. elegans ORFeome resource, generated using the Gateway cloning system, can be used to create alternative HT-RNAi resources with enhanced flexibility. This approach allows for gene knockdowns under various conditions, increasing the possibilities for phenome mapping. The ORFeome-RNAi v1.1 library contains 11,511 RNAi clones targeting 10,953 unique protein-encoding genes, representing an increase of ~9% in the total number of genes that can be targeted by RNAi-by-feeding. The authors performed a genome-wide RNAi screen in WT C. elegans hermaphrodites using this library and observed phenotypes for ~10% of the genes studied. They also discuss the reproducibility of the RNAi results and the factors affecting the frequency of phenotypes. The article concludes by emphasizing the value of an ORFeome-based approach for generating alternative HT-RNAi resources and improving phenome mapping in C. elegans.