Tablet is an effective system for delivering probiotics into the gastrointestinal tract. However, the mechanical stress, combined with the local heating generated during compaction, pose challenges to maintaining probiotic viability. Evaluating probiotic viability under various compression conditions is necessary to optimise the tabletting process. However, testing each scenario individually significantly increases development time and costs. Hence, it is of scientific and industrial importance to develop predictive models for assessing probiotic viability during compaction. In this study, a finite element (FE) model integrating the modified Drucker-Prager Cap (DPC) model with a thermal tolerance model was developed for the first time to predict the probiotic viability during powder compaction. The capability of the model in predicting mechanical behaviour, thermal response, and probiotic viability was demonstrated through comparison with experimental measurements. FE analysis revealed that the viability of the probiotic Lactobacillus gasseri (L. gasseri KS-13) decreases as the compression pressure increases, as observed experimentally. Furthermore, it is also found that pre-compression is an effective method to enhance the viability of probiotics during compaction.