It has been documented in several reports in the literatures, that study difficulty is associated with psychiatric morbidity. Most studies have also investigated the co-morbidity of either study difficulty and psychiatric morbidity or psychoactive substance use/abuse and psychiatric morbidity. This study aimed to determine the prevalence of a syndrome which consists of co-occurrence of study difficulty, psychoactive substance use/abuse and psychiatric morbidity among undergraduate senior students of University of Abuja. It also aimed to identify socio-demographic characteristics of students who suffer from this syndrome. In the study, six hundred and twenty four (624) students in 3rd and 4th year were sampled. The University College London Study Difficulty Questionnaire, World Health Organisation Questionnaire for Students Drug Use Survey and General Health Questionnaire (Version-30) were used to assess the prevalence of study difficulty, psychoactive substance use and psychiatric morbidity respectively. Prevalence rate of Brain Fag Syndrome was also determined using the Brain Fag Syndrome Scale. The findings from this study show that prevalence of the syndrome of co-occurrence of study difficulty, psychoactive substance use/abuse and psychiatric morbidity (termed ‘The Triad’) among senior students of University of Abuja was 16.7%, and this was associated with several socio-demographic factors. The study also revealed a highly significant positive association between ‘The Triad’ and Brain Fag Syndrome. The study showed that the components of this syndrome were major health problems for these students, and that the components interact very closely to the detriment of the mental health of the students. These findings indicate the urgent need to incorporate mental health services in the Health Services of our educational institutions, especially in tertiary institutions and for a co-ordinated approach by all the stakeholders to stem this vicious emerging trend (‘The Triad’).