We compute photoionization models for the giant extragalactic H II region NGC 5461 and compare their predictions to several observational constraints. Since we aim to reproduce not only the global properties of the region but also its local structure, the models are constrained to reproduce the observed density profile, and our analysis takes into consideration the bias introduced by the shapes and sizes of the slits used by different observers. We find that an asymmetric nebula with a Gaussian density distribution, powered by a young burst of 3.1 Myr, satisfactorily reproduces most of the constraints, and that the star formation efficiency inferred from the model agrees with current estimates. Our results strongly depend on the assumed density law, since constant-density models overestimate the hardness of the ionizing field, affecting the deduced properties of the central stellar cluster. We illustrate the features of our best model, and discuss the possible sources of errors and uncertainties affecting the outcome of this type of studies.