Water-soluble transition metals are more bio-accessible than insoluble particulate matter (e.g., PM2.5) components and can contribute to PM2.5 oxidative potential, a metric that has been linked to air pollution health impacts. Fifteen pairs of indoor-outdoor PM2.5 samples were collected outdoors and in unoccupied rooms to examine change of iron solubility and dithiothreitol-based oxidative potential of PM2.5 during outdoor-to-indoor transport. Changes of relative humidity (ΔRH = RHin/RHout - 1) and aerosol acidity (ΔpH = pHin/pHout - 1) together were found to modify iron solubility (ΔS = Sin - Sout) during outdoor-to-indoor transport. Multiple linear regression was performed to examine relationship between ΔRH, ΔpH and ΔS, resulting in a statistically significant correlation (correlation coefficient of 0.68 and P value < 0.05). This correlation coefficient is higher than that for ΔRH or ΔpH alone (0.40 between ΔRH and ΔS and −0.32 between ΔpH and ΔS). This supports that during outdoor-to-indoor transport, increases in RH lead to increases in water content in PM2.5, increasing the amount of iron in the aqueous phase, and decreases in pH would lead to stronger metal mobilization capacity. These two factors together explain the change of iron solubility during the transport process. A correlation coefficient of 0.67 was also found between ΔRH and ΔpH and changes in intrinsic oxidative potential (OPM) of PM2.5, further corroborating the combined role of relative humidity and aerosol acidity in driving change of iron solubility and OPM of PM2.5 during outdoor-to-indoor transport.