The present study uses a person-centered approach to examine how profiles of commitment, awareness, and openness to existential beliefs moderate the association between religious/spiritual (r/s) struggles and outcomes of well-being across two studies. Measures of existential humility, r/s struggles, and well-being were completed in a sample of undergraduates (Study 1, N = 303) and community members (Study 2, N = 1,027). Latent profile analyses (LPA) were conducted to identify profiles of existential humility (commitment, awareness, openness). The strength of associations between r/s struggles and well-being (i.e., Study 1: depression, anxiety, flourishing, meaning in life, life satisfaction; Study 2: death anxiety, meaning in life) were compared across profiles. Three profiles in Study 1 (i.e., Diffident Seekers, Arrogant Seekers, Moderates) and four profiles in Study 2 (i.e., Humble Seekers, Arrogant Seekers, Arrogant Dwellers, Moderates) significantly differed across outcomes of well-being in the face of r/s struggles. Results suggested that profiles higher in commitment and lower in existential humility (i.e., Arrogant Dwellers, Arrogant Seekers) showed vulnerabilities to depression and lack of meaning, whereas profiles higher in humility (i.e., Diffident Seekers, Humble Seekers) demonstrated vulnerabilities to anxiety. Profiles characterized by moderate commitment and existential humility (i.e., Moderates) showed relative advantages on outcomes of well-being. The findings suggest that the profiles of existential humility moderate the associations between r/s struggles and outcomes of well-being. This study demonstrates the value of taking a person-centered approach to assessing existential humility and its associations with well-being when individuals experience existential pain.