Substance abuse has greatly altered the moral and ethical standard as well as increase insecurity of our society. Hence, this research assessed knowledge and other factors influencing substance abuse among patients admitted to the two Neuropsychiatric Hospitals in South – West, Nigeria. A descriptive cross-sectional design was used. The purposive sampling method was utilized to collect data from 121 respondents from the two hospitals. Self- designed questionnaire was used as an instrument for data collection. Data were analyzed using SPSS version 23. The findings revealed chi – square value obtained for peer pressure is (X2 = 8.686, P = 0.034), personality trait (X2 = 11.222, P = 0.011), marital status (X2 = 31.455, P = 0.002) and occupation (X2 = 25.266, P = 0.046) at the significant levels less than 0.05 for the four variables respectively. Since these p – values were less than 0.05 value, it could be said that peer pressure, personality traits, marital status, and occupation have a significant relationship with substance abuse among patients in neuropsychiatric hospitals. The study concluded that Peer pressure, personality traits occupation, and marital status have influenced patients to substance abuse in the two neuropsychiatric hospitals but knowledge of substance abuse had no influence on substance abuse. Therefore, identifying specific factors that influence clients/patients to substance abuse during the assessment/interaction section may be helpful to give prompt/appropriate intervention that will be more effective.