The study determines how total quality management practices and good organizational culture will enhance operational performance in the banking sector in Ghana. The study is explanatory research design in nature. Taking the time frame of the study and the need to bring out a finding reasonable for generalization, the researcher selected a sample of 153. The findings of the study establish that total quality management has a positive and significant effect on service product innovation. Organizational culture has a positive and significant effect on service product innovation. Service product innovation has a positive and significant effect on firm performance. Organizational culture has a positive but insignificant effect on firm performance. Total quality management has a positive and significant effect on firm performance. The study further revealed that service product innovation positively and significantly mediates the relationship between total quality management and firm performance. The study finally assessed the mediating effect of service product innovation on the relationship between organizational culture and firm performance and the findings of the study indicate that service product innovation positively and significantly mediates the relationship between organizational culture and firm performance. How Total Quality Management practices and good organizational culture influence operational performance in the banking sector in Ghana.