Nuclear criticality safety assessment often requires groupwise Monte Carlo simulations of k-effective in order to check subcriticality of the system of interest. A typical task to be performed by safety assessors is hence to find the worst combination of input parameters of the criticality Monte Carlo code (i.e., leading to maximum reactivity) over the whole operating range. Then, checking subcriticality can be done by solving a maximization problem where the input-output map defined by the Monte Carlo code expectation (or an upper quantile) stands for the objective function or “parametric” model. This straightforward view of criticality parametric calculations complies with recent works in Design of Computer Experiments, an active research field in applied statistics. This framework provides a robust support to enhance and consolidate good practices in criticality safety assessment. Indeed, supplementing the standard “expert-driven” assessment by a suitable optimization algorithm may be helpful to increase the reliability of the whole process and the robustness of its conclusions. Such a new safety practice is intended to rely on both well-suited mathematical tools (compliant optimization algorithms) and computing infrastructure (a flexible grid-computing environment).