This review highlights recent advances in the synthesis of mesoionic precursors, mechanistic insights into carbene generation, and their growing role in homogeneous catalysis. Emphasis is placed on structure–reactivity relationships and emerging catalytic transformations that leverage the unique properties of mesoionic-derived NHCs. Mesoionic compounds have emerged as versatile and structurally unique precursors for the generation of N-heterocyclic carbenes (NHCs), offering distinct electronic properties compared to classical imidazolium-derived systems. Unlike traditional NHC precursors, mesoionic frameworks such as 1,2,3-triazol-5-ylidenes exhibit strong σ-donating and tunable π-accepting abilities, enabling enhanced stabilization of reactive intermediates in catalytic cycles. The inherent charge delocalization within mesoionic heterocycles facilitates facile carbene formation under mild conditions and expands the structural diversity of accessible ligands. These mesoionic NHCs demonstrate remarkable reactivity in transition-metal coordination chemistry and organocatalysis, supporting applications in cross-coupling reactions, olefin metathesis, C–H activation, and carbon–carbon bond formation. Furthermore, their steric and electronic tunability allows fine control over catalyst performance, including activity, selectivity, and stability.