Although empirical research demonstrates that personality predicts a significant amount of variance in work performance, studies using personality predictors are often criticized for having low criterion-related validities. A possible reason for this may be that personality dimensions are traditionally conceptualized as independent predictors (the variable-centered approach). However, this view does not take into account that individuals vary on multiple personality traits that exist concurrently (the person-centered approach). The present study addressed calls to combine Big Five personality traits into two-way interactions and profiles. The results were then used to compare whether the variable-centered or personcentered approach provides better predictions. The current study incorporated data from two samples. Participants for study 1 were 181 train operators. Participants for study 2 were 311 respondents recruited from Amazon Mechanical Turk. Contrary to previous research and expectations, the two-way interactions were not significant in either sample. However, more promising results were seen with the personality profiles. In study 1, latent profile analyses indicated a three profile solution that was consistent with well-established personality profiles. Such profiles significantly predicted rates of absenteeism when using 3-step mixture modeling. In study 2, latent profile analyses indicated a three profile solution that included two well-established personality profiles in addition to a new personality profile. These profiles predicted significant differences in citizenship performance, adaptive performance, and engagement when using both analyses of variance and 3-step mixture modeling. When comparing the approaches, the variable-centered approach fared better across analyses of covariance and in some cases when examining effect sizes. However, the person-centered approach produced more consistent effect sizes, which is promising for future investigations. The current study contained many advancements that can add to personality’s theoretical framework in personnel psychology, including the addition of the person-centered approach, usage of diverse outcome measures, and inclusion of the 3-step mixture modeling technique. Although more work is needed in order to understand if configural approaches can reliably be applied in personality research, the present study offers the first empirical comparison between these approaches across multiple job performance dimensions and multiple samples.