Objective To prepare poly (lactic-co-glycolic acid) (PLGA) based multifunctional nanoparticles loading with perfluoropentane (PFP), Mn (5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (MnTTP) and paclitaxel (PTX), and to investigate their ultrasound (US)/photoacoustic (PA)/magnetic resonance (MR) imaging enhancement capability and chemo-/sonodynamic therapy (SDT) efficacy in vitro. Methods PFP/MnTTP/PTX loaded in PLGA nanoparticles (termed as FMP@P) were prepared by a double emulsification method. The physical properties of FMP@P including average diameter, surface zeta potential, morphological character, drug loading efficacy and in vitro reactive oxygen species (ROS) generation were determined. In addition, the in vitro PA/US/MR imaging performance of FMP@P was observed and recorded. Upon US irradiation, intercellular ROS generation was investigated using confocal microscopy and flowcytometry. Meanwhile, the chemo-/sonodynamic therapy effect on 4T1 cell was evaluated by the standard CCK-8 assay and flow cytometry. Results The average diameter and zeta potential of FMP@P were (323.1 ± 68.3) nm and -(14.5 ± 8.3) mV. The loading efficiency of MnTTP and PTX was 93.55 ± 0.46% and 81.23 ± 6.93%, respectively. FMP@P enhanced US/PA/MR imaging. Upon US irradiation, FMP@P could produce a large amount of reactive oxygen species (ROS), which induced obvious cytotoxicity. Conclusion A multifunctional FMP@P were successfully fabricated, which enhanced US/PA/ MR imaging, mediated chemo-/SDT.