The study investigated the Influence of Management Information System (MIS) On the Management of Federal Universities in South-South Geopolitical Zone of Nigeria. Two research questions and hypotheses were raised to guide the study. The research design that guided the study was the cross-sectional survey research design. The population of the study consisted of 530 administrative staff. Census sampling technique was adopted to select the entire 530 administrative staff (376 males and 154 females). The researcher developed an instrument for data collection from the respondents. The instrument was tagged ‘Management Information System and Management of Universities Questionnaire’ (MISMUQ). Descriptive statistics of mean and standard deviation were used to answer the research questions while the independent t-test was employed to test the null hypotheses at 0.05 level of significance. The findings of the study showed that there is no significant difference on the mean responses of highly and lowly experienced staff on the influence of MIS on financial management of Federal Universities in South-South Geopolitical Zone of Nigeria and is no significant difference on the mean responses of male and female staff on the influence of MIS on staff management in Federal Universities in South-South Geopolitical Zone of Nigeria. The study recommended that the trainings should be organized by the management of universities for staff on how MIS can be used for effective financial management, as this would ensure that staff not only use MIS for word processing but also to store information of financial transactions that occur in the department, they work.