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Ọsẹ dúdú production and sale constitute a major indigenous business among the Yoruba people. Scholars have noted that the business is capable of boosting the socio-economic status of black soap entrepreneurs and of countries. However, ọsẹ dúdú enterprise has some significant threats and problems that are yet to be researched. This chapter examined the challenges of osẹ dúdú entrepreneurs in Southwest Nigeria. Twenty-six interviews were conducted among indigenous black soap producers and sellers in Ogun, Oyo and Lagos States. Data were analysed in themes. Weather, financial, spiritual, copyright and succession challenges, as well as issues such as a large number of sellers, debt, lack of support, pricing and brand competition, were found to be problems faced by black soap entrepreneurs. This chapter concluded that certain controllable and uncontrollable factors were not only capable of limiting the development of osẹ dúdú business but also have adverse implications for the achievement of the sustainable development goals through the indigenous resource. This chapter suggests that osẹ dúdú business actors such as mechanical engineers, local fabricators, financial institutions, and governmental and non-governmental agencies collaborate with black soap entrepreneurs to ameliorate the challenges of the latter. It is only through this alliance that black soap entrepreneurs can contribute to indigenous business development and the achievement of sustainable development goals in Africa.