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This study aimed to delineate various pathways whereby cognitive and emotional vulnerabilities triggered by stress would lead to disruptive gambling. A multiple mediation framework was proposed to specify that gambling cognition and subjective well-being would mediate the influence of perceived stress on problem gambling. The cross-cultural validity of the proposed framework was examined with 132 White gamblers in Australia and 154 Chinese gamblers in China. They completed psychological scales on perceived stress, gambling expectancy bias, gambling refusal efficacy, negative affect, life satisfaction, and problem gambling. Compared to Chinese gamblers, White gamblers reported higher levels of perceived stress, gambling expectancy bias, and problem gambling as well as more pervasive negative affect and lower levels of life satisfaction. Results showed that the proposed multiple mediation framework fit the data better than two alternative plausible models. Life satisfaction and gambling refusal efficacy were two consistent mediators across White and Chinese gamblers.