Understanding the potential socioeconomic losses due to natural hazards, such as earthquakes, is of foremost importance in the field of catastrophe risk management. The construction of a probabilistic seismic risk model is complex and requires the tuning of several parameters essential to represent the seismic hazard of the region, the definition of the exposed inventory characteristics, and its vulnerability to ground motion. Because significant uncertainties could be associated with each model component, the loss estimates are often highly volatile. Nevertheless, to reduce the conceptual complexity and the computational burden, in many real-life applications these uncertainties are either not adequately treated or neglected altogether. The false high fidelity of the ensuing loss estimates can mislead decision-making strategies. Hence, it is useful to assess the influence that the variability in the estimated values of the model input parameters may exert on the final risk results and their relevant contributions. To this purpose, we have performed a sensitivity analysis of the results of an urban seismic risk assessment for Isfahan (Iran). Systematic variations have been applied to the values of the parameters that control the earthquake occurrence in the probabilistic seismic hazard model. Curves of input–output relative variations were built for different risk metrics with the goal of identifying the parameters most sensitive to input uncertainty. Our findings can be useful to support risk managers and practitioners in the process of building seismic hazard and risk models. We found that the Gutenberg–Richter a and b values, the maximum magnitude, and the threshold magnitude are large contributors to the variability of important risk measures, such as the 475 yr and the average annual loss, with the more frequent losses being, in general, most sensitive.