The southern Peru and northern Chile coastal region is an active subduction zone that contains one of the most signifcant seismic gaps in the eastern Pacifc basin (~17°S–~24°S). Although the gap was partially flled by the 2014 Mw 8.1 Iquique earthquake, there is still a high seismogenic potential to release a Mw ~9 earthquake in the near future; therefore, all the near-feld coastal cities in the region face a latent tsunami threat. In this article, we propose a hybrid deterministic–stochastic multi-scenario approach to assess the current tsunami hazard level in the city of Iquique, an important commercial and industrial center of northern Chile that is home to 184,000 inhabitants. In our approach, we defned 400 stochastic, 10 deterministic and 10 homogeneous tsunamigenic earthquake scenarios, covering the entire area of the seismic gap. Based on the regional distribution of gravity anomalies and published interseismic coupling distributions, we interpreted the occurrence of four major asperities in the subduction interface of the seismic gap. The asperity pattern was used to construct a group of deterministic slip-defcit earthquake sources with seismic magnitudes ranging between Mw 8.4 and Mw 8.9. Additionally, we constructed 10 homogeneous slip scenarios to generate an inundation baseline for the tsunami hazard. Subsequently, following a stochastic scheme, we implemented a Karhunen–Loève expansion to generate 400 stochastic earthquake scenarios within the same magnitude range as the deterministic slip-defcit sources. All sources were used as earthquake scenarios to simulate the tsunami propagation and inundation by means of a non-hydrostatic model (Neowave 2D) with a classical nesting scheme for the city of Iquique. We obtained high-resolution data for fow depth, coastal surface currents and sea level elevation. The results suggest that the peak slip location and shelf resonance play an important role in the calculated coastal fow depths. The analysis of the entire set of simulated stochastic earthquake scenarios indicates that the worst-case scenario for Iquique is a Mw 8.9 earthquake. This scenario presented a tsunami arrival time of ~12 min, which is critical for the evacuation process. In addition, the maximum wave height and tsunami fow depth were found to be ~10 m and ~24 m, respectively. The observed coastal resonance processes exhibit at least three destructive tsunami wave trains. Based on historical and instrumental catalog statistics, the recurrence time of the credible worst-case earthquake scenario for Iquique (Mw 8.9) is 395 years, with a probability of occurrence of ~11.86% in the next 50 years.