A key issue affecting the performances of every human-conceived engineering system is its degradation, fatigue crack growth being one of the major structural deterioration phenomena. Fatigue crack growth is usually modelled as a stochastic process: uncertainty sources lie both in the item and in the physical degradation process variability. Fatigue crack growth deserves close attention, especially considering that condition-based maintenance methodologies are recently experiencing a major drive to increase their technology readiness level, requiring validated diagnostic and prognostic methodologies which should be capable of operating online and in real-time. In this regard, particle filters provide a consistent Bayesian framework, where the posterior distribution of the system degradation state is recursively approximated based on a time-growing stream of observations measuring the system response, enabling, in general, increasingly informed lifetime estimates. However, the real-time operation capability of such methods is hindered by their requirements in terms of computational power, which is mainly due to the complexity of the structural models they rely upon. Within this work, a comprehensive particle filter framework, able to deal with fatigue crack growth uncertainty sources while simultaneously addressing the computational burden issue, is proposed. The algorithm structure enables to simultaneously perform the diagnosis and prognosis of fatigue crack growth, while the adoption of the augmented state formulation allows to address scenarios where the degradation process of fatigue crack growth fails to meet the degradation model ruling the particle filter. Artificial neural networks–based surrogate modelling is adopted at different stages and embedded within the particle filter algorithm, relieving the computational burden associated with the evaluation of the trajectory likelihoods as well as enabling a fast estimation of the remaining useful life. Both simulated and experimental data sets regarding fatigue crack growth in an aluminium aeronautical panel are used for the algorithm testing, additionally proving the validity and effectiveness thereof by means of common prognostic performance metrics.