Aim: To establish the substance use pattern and psychological distress among the in-coming nursing students of the College with a view towards recommending ways to prevent or reduce complications of substance use disorder in the college. Study design: A cross-sectional design was used. Place and duration: The study took place at the College of Nursing and Midwifery, Jos, Plateau state between the 3rd and 14th of February, 2020. Methodology: The study was carried out during the orientation program of the 206 first-year students of the college. Following approval, a health talk and explanation of the aims and objectives, their consent was obtained in writing. Two-staged sampling with a sociodemographic questionnaire and Hopkins Symptom Checklist-25 followed by urine drug testing was done. The participants were debriefed on the findings while maintaining strict confidentiality. There were 65 males and 141 females. Results: Lifetime prevalence rate of any substance use was 21.8%. More females 33 (23.4%) than males 12 (18.5%) used substances. Only 9 (4.5%) volunteered their substance use, the rest was revealed by the urine testing. Prevalence of alcohol was 23 (11.2%), ketamine 13 (6.3%), nicotine 3 (1.5%), benzodiazepines 3 (1.5%), cannabis 2 (1.0%) and opiods 1 (0.5%). Symptoms of psychological distress were high as 118 (57.3%) and 82 (38.8%) were symptomatic for anxiety and depression respectively. Alcohol use was significantly related with having symptomatic anxiety (P = 0.02) and depression (P = 0.00) in the study. Conclusion: Considering the high prevalence of substance use among the participants, educational intervention and policies should be designed to prevent substance dependence with its complications within the students.