Subfamily Caesalpinioideae with ca. 4,600 species in 152 genera is the second-largest subfamily of legumes (Leguminosae) and forms an ecologically and economically important group of trees, shrubs and lianas with a pantropical distribution. Despite major advances in the last few decades towards aligning genera with clades across Caesalpinioideae, generic delimitation remains in a state of considerable flux, especially across the mimosoid clade. We test the monophyly of genera across Caesalpinioideae via phylogenomic analysis of 997 nuclear genes sequenced via targeted enrichment (Hybseq) for 420 species and 147 of the 152 genera currently recognised in the subfamily. We show that 22 genera are non-monophyletic or nested in other genera and that non-monophyly is concentrated in the mimosoid clade where ca. 25% of the 90 genera are found to be non-monophyletic. We suggest two main reasons for this pervasive generic non-monophyly: (i) extensive morphological homoplasy that we document here for a handful of important traits and, particularly, the repeated evolution of distinctive fruit types that were historically emphasised in delimiting genera and (ii) this is an artefact of the lack of pantropical taxonomic syntheses and sampling in previous phylogenies and the consequent failure to identify clades that span the Old World and New World or conversely amphi-Atlantic genera that are non-monophyletic, both of which are critical for delimiting genera across this large pantropical clade. Finally, we discuss taxon delimitation in the phylogenomic era and especially how assessing patterns of gene tree conflict can provide additional insights into generic delimitation. This new phylogenomic framework provides the foundations for a series of papers reclassifying genera that are presented here in Advances in Legume Systematics (ALS) 14 Part 1, for establishing a new higher-level phylogenetic tribal and clade-based classification of Caesalpinioideae that is the focus of ALS14 Part 2 and for downstream analyses of evolutionary diversification and biogeography of this important group of legumes which are presented elsewhere.