Nanoparticles (NPs) based techniques have shown great promises in all fields of science and industry. Nanofluid-flooding, as a replacement for water-flooding, has been suggested as an applicable application for enhanced oil recovery (EOR). The subsequent presence of these NPs and its potential aggregations in the porous media; however, can dramatically intensify the complexity of subsequent CO2 storage projects in the depleted hydrocarbon reservoir. Typically, CO2 from major emitters is injected into the low-productivity oil reservoir for storage and incremental oil recovery, as the last EOR stage. In this work, An extensive serious of experiments have been conducted using a high-pressure temperature vessel to apply a wide range of CO2-pressure (0.1 to 20 MPa), temperature (23 to 70 °C), and salinity (0 to 20wt% NaCl) during CO2/water interfacial tension (IFT) measurements. Moreover, to mimic all potential scenarios several nanofluids at different and NPs load were used. IFT of CO2/nanofluid system was measured using the pendant drop method as it is convenient and flexible technique, particularly at the high-pressure and high-temperature condition. Experimentally, a nanofluid droplet is allowed to hang from one end of a dispensing needle with the presence of CO2 at the desired pressure and temperature. Regardless of the effects of CO2-pressure, temperature, and salt concentration on the IFT of the CO2/nanofluid system, NPs have shown a limited effect on IFT reduction. Remarkably, increased NPs concentration (from 0.01 to 0.05 wt%) can noticeably reduce IFT of the CO2-nanofluid system. However, no further reduction in IFT values was noticed when the NPs load was ≥ 0.05 wt%. Salinity, on the other hand, showed a dramatic impact on IFT and also on the ability of NPs to reduce IFT. Results showed that IFT increases with salinity particularly at relatively low pressures (≤ 5 MPa). Moreover, increased salinity can eliminate the effect of NPs on IFT. Interestingly, the initial NP size has no influence on the ability of NPs to reduce IFT. Consequently, the potential nanofluid-flooding processes during EOR have no negative effect on the later CO2-geosequestration projects.