Alcohol and drug abuse among university students are significant public health concerns with multifactorial determinants. This study was carried out between Jan 2024 to June 20024 using multistage sampling technique to select the tertiary institutions and students. It aimed to investigate the influence of socio-demographic factors, peer pressure, family dynamics, and academic stress on substance abuse prevalence among students of the tertiary institution in Imo State, Nigeria. Method: A cross-sectional survey was conducted among 433 students using questionnaire to collecting data on socio-demographic characteristics, peer pressure, family dynamics, academic stress, and substance abuse behaviors. Chi-square tests were utilized to analyze the associations between variables, with p-values < 0.05 considered significant. Results: The results revealed that 59.9% of respondents reported that they never or rarely consuming alcohol, while 66.9% reported never using recreational drugs. Additionally, 62.7% of respondents reported not feeling pressured by peers to consume alcohol or use drugs. There were significant associations between peer pressure and socio-demographic factors, including age (X2 = 4.64, p = 0.031), gender (X2 = 0.01, p = 0.019), religion (X2 = 3.96, p = 0.046), monthly allowance (X2 = 7.42, p = 0.007), educational level (X2 = 8.19, p = 0.004), and residence (X2 = 11.37, p = 0.001). Additionally, family dynamics/upbringing (X2 = 33.2, p = 0.0101) and academic stress/workload (X2 = 11.5, p = 0.041) were significantly associated with substance abuse prevalence among students. Conclusion: The findings show high level in the knowledge of drug/substance abuse and the importance of addressing the socio-environmental determinants that contributes to alcohol/substance usage. Recommendations include implementing targeted prevention programs, strengthening family-based interventions, enhancing campus support services, promoting healthy coping mechanisms, providing education on substance abuse, conducting further research, and fostering collaboration and partnerships. By addressing these factors, universities can create supportive environments conducive to student well-being, ultimately mitigating substance abuse's negative consequences and promoting a culture of wellness and academic success.