Entrepreneurship and Vocational Education (EVE) has been considered as a vital key that opens the door of youth employment and employability in this 21st century. While several studies have been conducted to echo the importance and values of youth entrepreneurship and vocational education in Africa, there is dearth of research on challenges facing youths which constitute threats to their enrolment and completion rate in EVE. This study specifically examined the barriers to youth entrepreneurship and vocational education in Nigeria with a view to pointing the attention of governments, institutions and other stakeholders to these challenges. Descriptive research design of a survey type was used to carry out the study. One hundred and two (102) youths in various entrepreneurship and vocational skills acquisition programmes responded to the questionnaire designed to gather information which provided answers to the three (3) research questions raised in the study. Findings from the study revealed poor perception of EVE by the public, mismatch between training and labour market skill demand, and uncertainty of funding for self-establishment as the major barriers to EVE in Nigeria. The study recommends, among others, the training of Entrepreneurship and Vocational Education based guidance and counsellors by the universities who are not only skilled in different areas of EVE but also able to guide young people rightly towards choosing the right and relevant skill training that match the current labour market skill demand.