Abstract: Metal nanoclusters (NCs) are stable aggregates at the molecular level, consisting of several to hundreds of metal atoms bound together by physical or chemical interaction. These nanoclusters exhibit unique physicochemical properties that have garnered significant attention in various fields, including biology, catalysis, sensing, and drug delivery. In the field of catalytic reactions, atomically precise metal nanoclusters have acted as an archetypical model for elucidating the structural evolution and structure-property relationship of nanomaterials. However, due to the factors such as the uncertainty of the growth mechanism, the complexity of the crystallization process, and the inherent poor stability, the cluster research faces some challenges in the precise synthesis, structural analysis as well as the comprehension of catalytic reaction mechanism which hinder the full exploration and understanding of these fascinating properties of clusters. Recent years, mass spectrometry (MS) has emerged as a crucial tool in biomolecular analysis and the detection of organic reaction intermediates due to its high sensitivity, high resolution, and fast response. In cluster chemistry, the researchers have also introduced this technique into the study of metal nanoclusters with precise atomic numbers, which have played an important role in the synthesis of clusters and the analysis of their structures as well as reaction mechanisms. The ion source, as the "heart" of the MS, can ionize the analyte and then be detected by MS. Currently, the main ionization methods used for cluster analysis are electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). These two "soft" ionization techniques can obtain the quasi-molecular ion peaks of the clusters without destroying the structure of the clusters, thus determining the composition of the clusters. In addition, MS enables real-time characterization of the reaction process in solution, allowing for online monitoring of complex reaction components, providing an experimental basis for synthesis processes and catalytic reaction mechanisms of metal clusters. Notably, gas-phase ion-molecule reactions can provide catalytic primitive steps and reaction kinetics enabling in-depth analysis of microscopic reaction mechanisms at a strictly molecular level. For the structural characterization of clusters, tandem mass spectrometry (MS/MS) combined with quantum chemical calculation provides a powerful tool to study and understand the structural evolutions of clusters. By comparing and verifying the experimental and computational results, the correlation between the catalyst structure and its performance can be established, deepening our understanding of the catalytic reaction mechanism and process. This paper was focused on the latest development of soft ionization MS in monitoring intermediates of cluster synthesis, structure analysis, and catalytic reaction mechanism, and the emerging directions in this fascinating area of research were highlighted.