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This study examines resilience development to counter neuroticism's negative effects on life satisfaction. It focuses on self-compassion, coping flexibility, and trait resilience as mediators. Involving 215 U.S. college students, Structural Equation Modeling and the PROCESS macro in SPSS evaluated these effects. Results indicated a good model fit, with significant mediation by self-compassion, coping flexibility, and resilience, mitigating about 68% of neuroticism’s impact on life satisfaction. This reduced neuroticism’s influence to an insignificant level. The mediation effects remained stable under stress, anxiety, and depression, highlighting practical implications for psychological interventions to enhance life satisfaction and mental health for neurotic individuals.