Medicanes are mesoscale tropical-like cyclones that develop in the Mediterranean basin and represent a great hazard for the coastal population. The skill to accurately simulate them is of utmost importance to prevent economical and personal damage. Medicanes are fueled by the latent heat released in the condensation process associated with convective activity, which is regulated by the presence and activation of cloud condensation nuclei, mainly originating from sea salt aerosols (SSAs) for marine environments. Henceforth, the purpose of this contribution is twofold: assessing the effects of an interactive calculation of SSA on the strengthening and persistence of medicanes, and providing insight into the casuistry and sensitivities around their simulation processes. To this end, a set of simulations have been conducted with a chemistry-meteorology coupled model considering prescribed aerosol (PA) and interactive aerosol (IA) concentrations. The results indicate that IA produces longer-lasting and more intense medicanes. Further, the role of the initialization time and nudging strategies for medicane simulations has been explored. Overall, the results suggest that (1) the application of spectral nudging dampens the effects of IA, (2) the initialization time introduces a strong variability in the storm dynamics, and (3) wind-SSA feedback is crucial and should be considered when studying medicanes.