This study examined the influence of personality traits and religiosity on substance abuse among patients at the Federal Neuropsychiatric Hospital Treatment Centre, Maiduguri. The study was guided by three objectives which focused on determining the influence of personality traits on substance abuse, examining the influence of religiosity on substance abuse, and assessing the influence of personality traits and religiosity on substance abuse among patients. A descriptive survey design was adopted for the study. The population consisted of 177 participants, comprising (106) male and female (71) patients receiving treatment at the Federal Neuropsychiatric Hospital Treatment Centre, Maiduguri. Data were collected using structured questionnaires measuring personality traits, religiosity, and substance abuse behavior which demonstrated satisfactory psychometric properties. Regression analysis was used to test the hypotheses at 0.05 level of significance. The result of hypothesis one revealed that personality traits significantly influenced substance abuse among patients (R = 0.582, R² = 0.339, F (5, 143) = 14.45, p < .05). Conscientiousness (β = -0.25, p = .001) and agreeableness (β = -0.17, p = .021) significantly reduced substance abuse, while neuroticism (β = 0.29, p < .001) and extraversion (β = 0.13, p = .049) significantly increased substance abuse. Openness was not significant. Results of hypothesis two showed that religiosity significantly influenced substance abuse among patients at the Federal Neuropsychiatric Hospital Treatment Centre, Maiduguri (β = 0.342, t = 4.35, p < .05, 95% CI [0.23, 0.59).The study recommends that Government and hospital management should support multidisciplinary treatment approaches combining psychology, psychiatry, and spiritual counseling for effective rehabilitation outcomes.