Matrix-Assisted Laser Desorption/Ionization (MALDI) combined with tandem Mass Spectrometry (MS/MS) provides a powerful and versatile solution for the molecular characterization of synthetic macromolecules and polymeric materials as well as for imaging the composition and defects of solid polymer surfaces. The dispersive nature, high mass resolution and sensitivity of the Time-of-Flight mass analysis permit the comprehensive characterization of polymer mixtures and are ideally suitable for monitoring processes that cause even minor mass changes. The MS/MS arrangement allows for elucidation of copolymer sequences and differentiation of polymer architectures, such as macrocyclic vs. linear chains, or variously branched structures. The focusing ability of the laser also allows for the determination of the spatial distributions of analytes or imaging of defects on polymer surfaces. These advantages are further enhanced by interfacing MALDI-MS/MS with Trapped Ion Mobility (TIMS) separation that makes the differentiation of isobars and isomers possible and extends the applicability of MALDI-MS/MS to very complex polymeric mixtures. These advantages will be demonstrated with the precise structural analysis of a wide variety of synthetic materials, including large and crosslinked polymers and their dditives as well as synthetic polymer surfaces.