The antecedents of small and medium-sized enterprise (SME) techno-entrepreneurship such as mobile telephones, and broadband penetration, leapfrog development through technology intermediation and disruptive innovation in both developed and developing economies. The experience in sub-Saharan Africa (SSA) shows that these dynamics have strong effects in a region that lacks baseline infrastructure yet has a booming population of consumers that serves as catalyst for overall economic transformation. Through a review of formal academic scholarship and gray literature, including online reports, blogs, and articles, the present chapter conducts an exploratory study into key factors that drive the SSA techno-entrepreneurship experience. It also investigates challenges that should be priorities in strategy and policy formulation for the region to benefit from techno-entrepreneurship in the SME sector. The study suggests the implementation of strategies that will stimulate key sectors such as retail, health, education, and financial services where small and medium scale entrepreneurs play a dominant role in employment generation and creation of social and economic value. More importantly, governments in various SSA economies must be committed to driving science, technology, and innovation through partnership or direct involvement in the establishment of innovation centers, hubs, programs, and environments that foster a stronger ecosystem for technology entrepreneurship take-off.