In summary, the ion pair thermal model for MALDI MS is proposed. Key assumptions of the model include high temperature plume, gas phase thermal equilibrium, strong tendency to gas phase neutralization via ion pair formation and proton transfer, and overall plume charge neutral. The quantities of ions in the solid sample and in the gaseous plume were estimated. Ion yields were estimated based on gas phase thermal equilibrium at the macroscale level and at the individual ion pair level. The estimated ion yields were close to but might be somewhat lower than experimentally determined values depending on the assumption of plume temperature. One possible explanation for the lower than observed ion yields can be deviation of full thermal equilibrium of the actual plume. Besides ion yield estimation, the model can provide explanation of some observations in MALDI MS, which include detection of single-charged ions, roughly constant total number of ions, equal detection of positive and negative ions, reduction of metal adducts with ammonium salt and ion suppression. We hope that the new model can provide guidance on the design of new conditions and systems that can improve the performance of MALDI MS such as improving its sensitivity and resolution, and its ability and reliability for the analysis of large biomolecules.