This study investigated entrepreneurship opportunities and Nigerian graduates' unemployment in south-east and south-south geopolitical zones. The study adopted a survey-descriptive design because the events had taken place in their natural course of happening. Two hundred lecturers and Entrepreneurship Development Centers' Staff constituted the stratified random sample drawn from fifteen (15) tertiary institutions from the zones on which an 18-item Likert-type rating scale was administered for data gathering over a period of two weeks with the help of Field Research Assistants. The data were subsequently analyzed with the x2 test of Independence and Cramer's v-statistic to establish a basis for generalization of findings into the larger population as well as application of same to tertiary institutions in other geopolitical zones in Nigeria with the same characteristics as those that obtained in the two geopolitical zones under investigation. Findings revealed that (i) Government and its relevant agencies had taken significant actions to help Nigerian graduates establish enterprises as a strategy for creating employment, reducing poverty and controlling social vices. (ii) The various tertiary education, educational monitoring bodies and individual tertiary institutions significantly prepared Nigerian graduates to adequately identify existing and create new entrepreneurship opportunities. (iii) There was significant proof that Nigerian graduates have acquired necessary entrepreneurship skills for self-employment. One major recommendation was that Government should adopt the step-by-step Entrepreneurship Implementation Model designed by the researchers for effective solution of the problems investigated and reported in this paper.