The existence of cancer and its continuous threat to life demands extensive therapeutic research. Moreover, there has been a drastic increment in newer cancer cases every year around the world, which advocates a unique way of improving cancer treatments. Recently, magnetic fluid hyperthermia (MFH) has received significant attention in cancer nano-therapeutics, and it allows us to be symbiotically utilized with other modalities such as chemotherapy to enhance treatment efficacies. However, numerous challenges must be needed to overcome in clinical hyperthermia scenarios such as higher heat-inducing property & therapeutic efficacy with (i) minimal concentration of therapeutic agents to prevent acute toxicity, and also (ii) tolerable MFH strength & frequency to evade needless side effects on the patients. To address these current challenges, in this work superparamagnetic iron oxide nanoparticles (SPIONs) and dual-drugs (nifedipine (a calcium channel blocker) & curcumin) are co-encapsulated in a step-wise manner inside d-ɑ-tocopheryl polyethylene glycol succinate (TPGS)-stabilized poly(d,l-lactide-co-glycolide) (PLGA-a polymeric nanocarrier) nanoparticles (TP-NPs). Herein, significant attention has been given to balancing both the safety and therapeutic effectiveness by optimizing the concentrations of dual drugs, SPIONs & also nanocarriers (i.e., TP-NPs), and also applied alternating magnetic field (AMF). The SPIONs inside TP-NPs have exhibited improved magneto-thermal effects (i.e., measured in terms of specific absorption rate (SAR) = 62.8–72.0 W/gFe) under an applied AMF. As a result of these improved effects via SPIONs, dual drugs are effectively released (almost ∼90 \% in a time-dependent manner) and concentrated highly inside the HepG2 cancer cells. Consequently, the in vitro thermo-chemotherapy studies have shown enhanced inhibition rates (up to 89 \%) in the growth of HepG2 cancer cells at a very less concentration (i.e., 0.5 mgFe). The results obtained from the present study are compared with previous reports, which have indicated that magneto-drugs encapsulated polymeric nanocarriers (i.e, TP-NPs) prepared in this work are highly promising in improving the cancer treatment efficacy by producing an extensive symbiotic effect. © 2020 Elsevier B.V.