Contagious diseases are constantly affecting more and more people every day, resulting in widespread health crises especially in developing nations. Previous studies have developed deterministic and stochastic mathematical models to investigate the spread of epidemics. In the present study, a hybrid particle filtering epidemiological model is proposed, which combines the elements of a deterministic susceptible-exposed-infectious-recovered-deceased (SEIRD) model with the inclusion of stochastic and penalty factors, in order to efficiently evaluate the dynamics of the disease. The inclusion of penalty factors stands out as the main novelty of the proposed methodology, guaranteeing estimations that align with the unique aspects of the examined natural phenomenon. The model is applied to the monkeypox (mpox) data of the United States from June 25th to November 21th, 2022. Our approach is compared to four alternatives, corresponding to deterministic and stochastic approaches that are associated with either fixed or time-varying parameters. In all cases, the particle filtering models displayed better characteristics in terms of infectious cases and deaths compared to their deterministic counterpart. The final version of the proposed epidemiologically informed particle filtering (EI-PF) model exhibited significant potential and provided the best fitting/predictive performance compared to other examined methodologies. The predictive effectiveness of the proposed methodology has been thoroughly evaluated across various time intervals. Moreover, the inclusion of additional penalty factors in the weight computation procedure, assists in reducing fitting and prediction errors while simultaneously providing increased likelihood estimates. This modelling approach can be readily applied to other epidemics, both existing and emerging, where uncertainties in system dynamics and real-time observations hinder the accurate capture of the epidemic's progression.