Street food vendors (SFVs) are highly self-governing and play their own role in reducing unemployment, crime and generate income for their survival. Moreover, SFVs are more accessible and affordable for the urban poor. However, they are not given due attention and support by concerned bodies in the creation of enabling environment. The study intended to investigate the challenges of SFVs in Mekelle city. In achieving the objectives of the study, both primary and secondary data were used. Primary data were collected from SFVs and managers of small scale enterprise of sub cities and secondary data were gathered from relevant reports and published materials. 384 sample SFVs were surveyed from Hawlti, Kedamayeweyane and Adi-Haki sub cities and stratified random sampling and convenience non random sampling were employed to select sample SFVs respondents. Descriptive statistical tools were used to present and analyze the data collected. The finding of the study depicted that SFVs face operational, managerial and governmental challenges during the operations and running of their business. Therefore, provide favorable working premises, design appropriate policy framework that support SFVs (designing legally supporting framework), and providing training are recommended.