This study evaluated the cost-benefit effectiveness of biotechnology solutions in reducing postharvest losses among smallholder farmers in Southwest Nigeria. A descriptive survey design was employed, with 500 farmers sampled through proportional stratified random sampling, of which 400 valid responses were analysed using descriptive statistics, cost-benefit ratios (CBR), paired sample t tests, linear regression, and ANOVA at a 0.05 significance level. Findings revealed that adopting biotech interventions such as genetically modified crops, microbial bio-preservatives, hermetic storage, and mobile-based advisory services led to a marked reduction in postharvest loss rates (27.4% to 11.8%). Hypothesis testing showed a significant difference in pre- and post-adoption loss rates (t = 199.385, p < 0.001) and a positive relationship between biotech adoption and postharvest income (β = 1.545, p < 0.001). However, the type of biotech solution did not significantly influence income (F = 2.575, p = 0.077). These findings demonstrate that biotechnology adoption enhances profitability, reduces spoilage, and strengthens household economic resilience. The study recommends extending extension services, subsidising biotech inputs, and integrating postharvest biotechnology into state agricultural policies to promote wider adoption and sustained impact.