Providing safe and secure food for an increasing number of people globally is challenging. Coping with such a human population by merely applying the conventional agricultural production system has not proved to be agro-ecologically friendly; nor is it sustainable. Cowpea (Vigna unguiculata (L) Walp) is a multi-purpose legume. It consists of high-quality protein for human consumption, and it is rich in protein for livestock fodder. It enriches the soil in that it recycles nutrients through the fixation of nitrogen in association with nodulating bacteria. However, the productivity of this multi-functional, indigenous legume that is of great value to African smallholder farmers and the rural populace, and also to urban consumers and entrepreneurs, is limited. Because cowpea is of strategic importance in Africa, there is a need to improve on its productivity. Such endeavors in Africa are wrought with challenges that include drought, salinity, the excessive demand among farmers for synthetic chemicals, the repercussions of climate change, declining soil nutrients, microbial infestations, pest issues, and so forth. Nevertheless, giant strides have already been made and there have already been improvements in adopting sustainable and smart biotechnological approaches that are favorably influencing the production costs of cowpea and its availability. As such, the prospects for a leap in cowpea productivity in Africa and in the enhancement of its genetic gain are good. Potential and viable means for overcoming some of the above-mentioned production constraints would be to focus on the key cowpea producer nations in Africa and to encourage them to embrace biotechnological techniques in an integrated approach to enhance for sustainable productivity. This review highlights the spectrum of constraints that limit the cowpea yield, but looks ahead of the constraints and seeks a way forward to improve cowpea productivity in Africa. More importantly, this review investigates applications and insights concerning mechanisms of action for implementing eco-friendly biotechnological techniques, such as the deployment of bio inoculants, applying climate-smart agricultural (CSA) practices, agricultural conservation techniques, and multi-omics smart technology in the spheres of genomics, transcriptomics, proteomics, and metabolomics, for improving cowpea yields and productivity to achieve sustainable agro-ecosystems, and ensuring their stability.