In experimental studies using the cue reactivity paradigm (CRP), classically conditioned substance craving is well-documented among individuals who use substances with trauma histories. However, the magnitude of this effect has not yet been quantified, nor have moderators of this relationship been identified [DeGrace, S., et al. (2022). IntechOpen. https://doi.org/10.5772/intechopen.103816]. While the mechanism driving these trauma cue-induced craving effects has been suggested to involve trauma cue-induced negative affect [Baker, T. B., et al (2004). Addiction motivation reformulated: An affective processing model of negative reinforcement. 111(1), 33-51. https://doi.org/10.1037/0033-295X.111.1.33], this remains largely untested. We conducted a meta-analysis to quantify the trauma cue-induced craving effect size, as well as possible moderators of these effects. Moreover, we utilized two-step meta-analytic structural equation modelling (TS-MA-SEM) to test the indirect effect of trauma (vs. neutral) cue exposure on substance craving through negative affect as the mediator. Our literature search returned  = 32 studies involving a total of  = 21 unique datasets that were included in our analyses. Results supported our hypothesis that trauma cues would induce greater substance craving relative to other cue types/controls (neutral cues, substance cues, pre-cue baseline), with small to medium effect sizes ( = 0.259 - 0.526). We found a few theoretically relevant moderators (CRP method, study quality, and % of sample with PTSD) that varied by comparator condition. Additionally, results supported our proposed mediational model with negative affect indirectly explaining the relationship between trauma cue exposure and substance craving. Results suggest that trauma cue-elicited substance craving is a robust phenomenon that may be explained through trauma cue-induced negative affect driving increased craving.