The aim of this research was to investigate the efficiency of microwaves (MW) for wine microbiological stabilization and thereby assess the potential application of a Weibullian mathematical model in wine industry. The study focused on (i) the influence of treatment time (come-up time and temperature maintenance) and temperature on a simple wine-like matrix, as well as (ii) the specific resistance of yeast and bacteria selected according to their representativeness in red wines (A. aceti ATCC_15973, S. cerevisiae FX10, B. bruxellensis CRBO_L0619 and AWRI_1499), and finally (iii) the potential usefulness of a new mathematical model adapted to heat treatment to evaluate strain sensitivity. This research aimed to show that microwave treatment decreases the main wine-associated microorganism populations and that the reduction in viable counts mainly depends on the MW treatment temperature. Complete microbiological stabilisation was obtained under a temperature of 50 °C a very short treatment time, except in the case of A. aceti ATCC_15973. Furthermore, the Weibull parameters analyses showed that heat inactivation a wine microorganism studied did not follow first-order kinetics, indicating that we should change our way of studying thermal death curves. The findings from this study suggest that MW could be useful for the wine industry as a complement or an alternative to sulphite utilisation.