In relation to its rapid infrastructure expansion, exemplified by projects like the Najran Valley Dam or the rehabilitation of agricultural terraces, Saudi Arabia stands out among the Arabian Gulf nations. To mitigate the earthquake-related risks effectively, it is imperative to conduct an exhaustive analysis of its natural hazards. The southwesternmost region of Saudi Arabia is the main subject area of this study for the probabilistic seismic hazard assessment (PSHA), which aims to identify the peak ground acceleration (PGA) and spectral acceleration (SA) values. The investigation encompasses a 10% and 5% probability of occurrence over a 50-year exposure time for both B/C and C NEHRP soils. In order to take into account the earthquake activity that takes place in the vicinity of the Red Sea Rift, which in fact may have an impact on the seismic hazard in this active tectonic region, different seismic source zones were especially designed for this evaluation. Various characteristics such as the uncertainties related to the b-value, the expected maximum magnitude, and different ground motion prediction equations (GMPEs) were integrated using a logic tree scheme. Additionally, regression relationships between the computed ground motion values were established, and a novel design response spectrum was developed and recommended for several cities. Regarding the key findings, it is significant to highlight that the seismic hazard decreases towards the northeast, when moving away from the Red Sea Rift, confirming anticipated trends where proximity to the rift corresponds to increased seismic hazard. Notably, cities such as Farasan Island, Jazan, Al Qunfundhah, Al Lith and Al Birk present the highest observed hazard values among all the cities analyzed. For these cities, the obtained maximum SA values for both 475 and 975 years under B/C site conditions are as follows: 0.268 g and 0.412 g, 0.121 g and 0.167 g, 0.099 g and 0.150 g, 0.083 g and 0.135 g, and 0.066 g and 0.118 g, respectively. These results emphasize the crucial necessity of adequately evaluating and thoroughly updating the seismic hazard inherent to these particular areas to enhance the risk reduction and disaster readiness initiatives. [ABSTRACT FROM AUTHOR]