Explosive loading in a confined internal environment is highly complex and is driven by nonlinear physical processes associated with reflection and coalescence of multiple shock fronts. Prediction of this loading is not currently feasible using simple tools, and instead specialist computational software or practical testing is required, which are impractical for situations with a wide range of input variables. There is a need to develop a tool which balances the accuracy of experiments or physics-based numerical schemes with the simplicity and low computational cost of an engineering-level predictive approach. Artificial neural networks (ANNs) are formed of a collection of neurons that process information via a series of connections. When fully trained, ANNs are capable of replicating and generalising multi-parameter, high-complexity problems and are able to generate new predictions for unseen problems (within the bounds of the training variables). This article presents the development and rigorous testing of an ANN to predict blast loading in a confined internal environment. The ANN was trained using validated numerical modelling data, and key parameters relating to formulation of the training data and network structure were critically analysed in order to maximise the predictive capability of the network. The developed network was generally able to predict specific impulses to within 10% of the numerical data: 90% of specific impulses in the unseen testing data, and between 81% and 87% of specific impulses for data from four additional unseen test models, were predicted to this accuracy. The network was highly capable of generalising in areas adjacent to reflecting surfaces and as those close to ambient outflow boundaries. It is shown that ANNs are highly suited to modelling blast loading in a confined internal environment, with significant improvements in accuracy achievable if a robust, well distributed training dataset is used with a network structure that is tailored to the problem being solved.