The advanced fabrication and surface engineering of superparamagnetic iron oxide nanoparticles (SPIONs) could offer excellent physiochemical features for noninvasive tumor imaging and drug delivery. The key issues of realization of maximized selective cancer targeting of SPIONs are minimization of uptake by macrophages, preferential binding to cancerous cells over neighboring normal cells, visualization of tumor cells prior to and after treatment and triggered drug release into target cells in a controlled fashion. In this article, we summarize the current status of fabrication of multifunctional SPION-based nanodevices specially designed for cancer-oriented diagnosis and therapy, with a focus on potential malignancy-targeting ligands' identification and development as nanocarriers. A number of examples of passive and active targeting strategies--lymphoangiogenesis markers, cellular metabolite receptors, extracellular matrix component receptors, neuropeptide receptors and receptor-mediated bypass of the blood-brain barrier--are described in detail.