In this work, we have developed novel multifunctional magnetic-polymeric nanoparticles (MMPNs) based ferrofluids by encapsulating oleylamine (OM)-coated hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) inside the poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) individually, and along with two drugs such as curcumin (Cur, a chemotherapeutic drug (CHD)), and/or verapamil (Ver, a calcium channel blocker (CCB)). Herein, several parameters such as weighed amount (wt\%) of PLGA polymer (i.e., Resomer), stabilizer (i.e., polyvinyl alcohol (PVA)), organic solvents, amount of the SPIONs (in liquid suspension and powder forms), and amount of the drugs (i.e., Cur or/and Ver) are varied during the encapsulation process to optimize the formulation of PLGA NPs. The resulting polymeric NPs including empty PLGA NPs (i.e., without SPIONs/drugs), and MMPNs such as SPIONs-loaded PLGA NPs, Cur-SPIONs-loaded PLGA NPs, Ver-SPIONs-loaded PLGA NPs, and Cur-Ver-SPIONs-loaded PLGA NPs have displayed (i) hydrodynamic diameters and zeta potentials in the range of 280.8–287.3 nm, and −21 to – 26 mV, respectively, and (ii) better encapsulation efficiency for the SPIONs/Cur/Ver. In addition, the MMPNs have exhibited (i) magnetization values in the range of 7.6–9.5 emu/g with superparamagnetic behaviour, (ii) concentration based time-dependent temperature raise up-to 42 °C (minimum therapeutic temperature in magnetic fluid hyperthermia (MFH)/thermotherapy) with heating efficacies i.e., specific absorption rate (SAR) and intrinsic loss power (ILP) values ranging from 7 to 36 W/gFe and 0.1–0.4 nHm2/kg, respectively and (iii) better cytocompatibility. Finally, the SPIONs and dual-drugs (Cur &Ver) co-loaded PLGA NPs have shown enhanced therapeutic efficacy in HepG2 cancer cells via combined therapies (i.e., thermotherapy and chemotherapy), as compared to the individual therapy (i.e., thermotherapy or chemotherapy) using the SPIONs/Cur/Ver loaded PLGA NPs. Thus, the as-prepared SPIONs/dual-drugs co-loaded PLGA NPs (i.e., MMPNs based ferrofluids) are potential therapeutic candidates for multi-modal treatment of cancer in vitro using thermotherapy and chemotherapy. © 2019 Elsevier B.V.