Tilapia production in most Southern African countries has remained low despite the high potential that exists. This sector is particularly important for inland countries. Government and donor driven programmes have largely failed to boost tilapia production in the last four decades in most Southern African countries. However, Zambia has experienced significant growth in tilapia production in recent years. In other Southern African countries namely, South Africa, Namibia, Botswana, Mozambique, Malawi, and Eswatini tilapia production has remained low. In this paper the physical, biological, and socio-economic factors that have affected tilapia production in the region are identified. Intervention measures are suggested. Economic factors, the choice of the tilapia species and the production system to be used were identified as the key factors affecting tilapia production in the region. The overriding factor affecting tilapia aquaculture production in Southern Africa is the lack of profitability. Tilapia culture is not profitable because of the cheaper wild caught tilapia and the Chinese imported tilapia. A paradigm shift in the way aquaculture is viewed is necessary. Instead of looking at aquaculture as a poverty alleviation tool it must be viewed as a business. A new approach in the training of fish farmers at a regional level is also suggested.