Conventionally, researchers have favored the model-based control scheme for controlling gantry crane systems. However, this method necessitates a substantial investment of time and resources in order to develop an accurate mathematical model of the complex crane system. Recognizing this challenge, the current paper introduces a novel data-driven control scheme that relies exclusively on input and output data. Undertaking a couple of modifications to the conventional marine predators algorithm (MPA), random average marine predators algorithm (RAMPA) with tunable adaptive coefficient to control the step size ( CF) has been proposed in this paper as an enhanced alternative towards fine-tuning data-driven multiple-node hormone regulation neuroendocrine-PID (MnHR-NEPID) controller parameters for the multi-input–multi-output (MIMO) gantry crane system. First modification involved a random average location calculation within the algorithm’s updating mechanism to solve the local optima issue. The second modification then introduced tunable CF that enhanced search capacity by enabling users’ resilience towards attaining an offsetting level of exploration and exploitation phases. Effectiveness of the proposed method is evaluated based on the convergence curve and statistical analysis of the fitness function, the total norms of error and input, Wilcoxon’s rank test, time response analysis, and robustness analysis under the influence of external disturbance. Comparative findings alongside other existing metaheuristic-based algorithms confirmed excellence of the proposed method through its superior performance against the conventional MPA, particle swarm optimization (PSO), grey wolf optimizer (GWO), moth-flame optimization (MFO), multi-verse optimizer (MVO), sine-cosine algorithm (SCA), salp-swarm algorithm (SSA), slime mould algorithm (SMA), flow direction algorithm (FDA), and the formally published adaptive safe experimentation dynamics (ASED)-based methods.