This study aimed to identify fertilization options for improving cassava productivity and profitability in two contrasting regions of the Central African Republic. The Pissa (guinea forest) and Damara (savannah). The study adopted a randomized complete block design with four treatments replicated four times in a plot size of 7 m by 7 m. The treatments were; T1 (Control), T2 (Peasant practice), T3 (sole NPK), and T4 (Cow manure+NPK). We performed the analysis of variance (ANOVA) using R statistical software version 3.1.2. The yield attributes and growth parameters significantly varied (p=0.05) with application of NPK and NPK plus manure. The use of 3 t ha -1 of cow manure and 90N-30P-180 Kg ha -1 of mineral fertilizer gave the highest yield of 50 and 37 t ha -1 in Pissa and Damara respectively compared to their local controls (no input); This combination also resulted in high profitability with high value-tocost ratios (RVC = 2 in Pissa and 1.3 in Damara). The variability study (48.11%) showed a correlation between growth and production parameters; the effects of fertilizers were much more expressed in the plant's circumference and the number of leaves. The use of organo-mineral fertilizer can give good productivity and profitability. Thus, T4 is a technology that resource-poor households can easily use, although the purchasing power of the peasant farmers in the study area is low.