This chapter investigates the opportunities and challenges related to KBUD found in Cairo's informal settlements. Also, it explores the ability of KBUD approach in dealing with the development of such settlements instead of the adopted approaches which failed in approaching the economic aspect within these communities. The chapter provides insights on the important role KBUD could play not only in the economic growth of richer and more prestigious contexts but also in poor communities which have a lot of hidden potentials. Accordingly, the chapter investigates Cairo's informal settlements, the policies and approaches used and applied, and the related defects and shortcomings. Then, it explores the theoretical framework of KBUD. Following this, opportunities and challenges related to KBUD in Cairo's informal settlements are discussed. By the end, the chapter sheds light on some points and concludes with recommendations for readapting KBUD approach when developing Cairo's informal settlements.