Failure of cancer therapy is typically associated to the poor accumulation of chemotherapeutics in tumor cells, the development of multidrug resistances, and the severe side effects. To beat the challenge, combined therapies against malignancies based on biodegradable nanosystems have emerged. Here, it is described the reproducible formulation of ≈ 270 nm-sized magnetic multicore PLGA particles. Characterization of the nanostructures by dynamic light scattering, electron microscopy, goniometry and electrophoresis confirmed the inclusion of hydrophobic maghemite nuclei in a polymeric nanomatrix. Adequate magnetic responsiveness was determined in vitro, while colloidal stability at 4 °C was demonstrated in short-term stability tests. Under the influence of an alternating electromagnetic field, the maghemite/PLGA (core/shell)-based colloid reached the minimum temperature of hyperthermia (≈ 42 °C) in ≈ 30 min. These heating capabilities made possible a significant decrease in the viability of T-84 cells (to ≈ 43 %). Finally, Cisplatin loading to the magnetopolymeric nanoparticles was characterized quantitatively by UV–Vis spectrophotometry (entrapment efficiency ≈ 82 %), and qualitatively by electrophoresis. The resulting Cisplatin-loaded magnetic multicore PLGA particles demonstrated a superior antitumor activity over the free chemotherapeutic in A-549 cells. These core/shell particles could be of interest for hyperthermia cancer treatment and chemotherapy.