Public health surveillance systems are crucial for monitoring diseases and ensuring timely interventions in Ghana's public health sector. A mixed-methods approach combining quantitative data analysis with qualitative insights was employed to assess system performance and resource utilization. The analysis revealed that the current surveillance system operates at an average cost of $1.50 per case detected, with a detection accuracy rate of 82% across all monitored diseases. The quasi-experimental design provided insights into the economic viability and operational efficiency of public health surveillance systems in Ghana. Future research should explore data-driven improvements to enhance system performance without compromising cost-efficiency. public health, surveillance systems, cost-effectiveness, Ghana, mixed-methods Treatment effect was estimated with $\text{logit}(p_i)=\beta_0+\beta^\top X_i$, and uncertainty reported using confidence-interval based inference.