The Nigerian-South African relationship is couched in the paradigm of intricate interdependence. The elements that brought the two African major powers closer include political, cultural, and economic dimensions. Therefore, any dissimilarity of interest between both countries would ruin their relationship and implicate the whole African Union concept that unites Abuja/Pretoria relations. Over 100 South African companies permeate the Nigerian market in several economic sectors and most are successfully operating in Nigeria. Nigerian companies such as First Bank, among others, are also operating in South Africa. As long as South Africa and Nigeria are both dominant powers in their respective sub-regions, a threat like xenophobia needs to be eradicated and coordinate some effective policies for Africa's development. The study employed a qualitative method and library sources, past literature on different xenophobic trends noted in the journal articles, books, and others, on the South African xenophobia and its implications on Nigeria/South African relationship. The study adopted the frustration-aggression theory and it found that incessant xenophobic attacks on Nigerian nationals and other foreigners in South Africa are based on prejudices. The study went further with suggestion to provide some panacea to the catastrophe of South African xenophobia.