Billions of dollars paid by industries on catalysts used as feedstocks to obtain their end products are increasing at a geometrical rate, the report revealed that the global marketplace price of catalysts stood at USD 26.1 billion in 2019, and is anticipated to increase by 4% in 2020, and 4.5% progress rate in 2025. To salvage the world from extravagance spending, there is an urgent need for biomass wastes consideration and utilization. In this paper, three novel CaO-based catalysts derived from Theobroma cacao pod husks were tested based on efficacy for the production of biodiesel (fatty acid ethyl ester: FAEE) from the blend of beef tallow-waste use oil in the ratio of 5:95 (BTO5),10:90 (BTO10),15:85 (BTO15), 20:80 (BTO20),….., 95:5 (BTO95), respectively. Process optimization of the transesterification reaction was carried out using a hybrid design to determine the effects of catalyst on the FAEE yield. The efficiencies of the catalyst were tested via the refining and reusability test. Results revealed the oil blend ratio of BTO60: WUO40 sufficiently produced low viscous oil that was easily converted to biodiesel. Catalysts' characterization revealed the three catalysts produced high CaO-based of 68.20, 81.46, and 87.65 (wt.%), which accounted for the high yield of FAEEs.Mathematical optimization showed that the catalyst amount (F-value between 14159.69-3063.24 with P-value between 0.0053-0.0115), played the most significant role in oil conversion to biodiesel among the constraint factors considered (reaction time, catalyst amount, reaction temperature, and EtOH/OMR).Based on Box-Cox transformation, the values of the lambda obtained indicated a normal data results with an inverse function of Y2 and Y3 and normal function of Y3 for polynomial model accuracy. Optimum validated FAEEs yields of 92.81, 93.02, and 99.64 (%wt.), respectively, with high R2. The qualities of the FAEEs were within the standard specification and the produced catalysts can serve as feedstocks for industrial application.