5A06-O and 2219-T87 aluminum alloys are promising candidates for propellant tanks. In this study, refill friction stir spot welding (refill FSSW) with a 0.1 mm offset was applied to produce defect-free 5A06-O/2219-T87 welds. A Box-Behnken method and statistical analysis were used to optimize the processing parameters, by determining the influence of welding parameters on lap shear strength (LSS). Plunge depth was the most influential parameter on LSS. All joints failed through the weld seam, including those tested at −55 °C. Microhardness measurements showed a slight increase in the 5A06 sheet over time, while the 2219 sheet exhibited significant hardness reduction. Microstructural analysis revealed typical features of refill FSSW, including a heat-affected zone, thermo-mechanically affected zone, stir zone, hook, and joint-line remnants. Novel findings include the identification of an onion structure in the welds, characterized by fine equiaxed grains and nanoprecipitates that contribute to weld's hardness. This unique microstructure, formed under the thermal and mechanical conditions of the FSSW process, strengthens the material and enhances its mechanical performance. Stop-action tests provided insights into material flow and microstructural evolution during welding. While conventional refill FSSW could not produce defect-free welds, the findings highlight the potential of the 0.1 mm offset refill FSSW to enhance weld quality, supporting its application in aerospace components requiring high mechanical integrity across extreme temperature ranges.