Biodiesel and n-butanol, as popular alternative fuels, can be used in advanced reactivity-controlled compression ignition (RCCI) engines for efficient and clean combustion. However, the complex interactions between n-butanol and biodiesel, as well as the best combustion schemes at different loads, remain poorly understood. Given this, the objective of this paper is to identify optimal fuel organizations for n-butanol/biodiesel RCCI engines across different load scenarios by combining engine simulation with a global optimization algorithm, explore the potential synergies of control parameters, and analyze microscopic dual-fuel interactions based on the integrated average reaction path analysis. Results show that the optimal scheme at low load employs almost homogeneous fuel-air mixtures at elevated temperature atmosphere above 390 K, with n-butanol energy share exceeding 96% and optimal biodiesel injection timing between −70 and −50 °CA. Higher n-butanol ratio coupled with increased intake temperature improves engine performance. For mid load, biodiesel injection timing is retarded to −55 to −30 °CA, and biodiesel proportion is increased to introduce reactivity stratification, while maintaining its energy share below 20% to mitigate NOx emissions. Notably, biodiesel density is identified as the primary physical property influencing NOx formation. At high load, a split combustion scheme involving premixing and subsequent diffusion combustion is optimal. The physical effects of n-butanol addition minimally impact the low-temperature ignition of biodiesel, while its chemical effects significantly defer the low-temperature reactivity. The reaction path analysis reveals that n-butanol competes with biodiesel for OH radical consumption, with a large proportion of OH and HO2 consumed in the cyclic reactions of nC4H9OH and nC4H8OH. Adjusting the reactivity stratification affects the reaction state of n-butanol entrained by the biodiesel jets. Higher reactivity gradient intensifies biodiesel reactions to induce the pyrolysis of the involved n-butanol through nC4H8OH => 2C2H4 + OH, therefore resulting in more staged heat release.