Low solubility in water is an intrinsic property of many drugs, which hinders the clinical use of those active ingredients. To break this bottleneck, we attempt to develop an iron oxide nanoparticle-based multifunctional system. Firstly, we perform PEG coating and compare the feasibility of spherical and rod-like iron oxide nanoparticles in a view of carcinoma cellular uptake; rod-like nanoparticles attracted our interest since they could be quickly and massively internalized. For paclitaxel (PTX) loading, we next transform the nanorods into a tube structure by a hydrothermal method. The results show that drug crystals can be successfully loaded in the inner voids of these nanotubes (PMNTs) by controlling the crystallization process of PTX. The acquired nanocomplexes not only escape phagocytosis of macrophage cells by a PEG stealth effect, but also exhibit an increased cellular uptake with magnetic field exposure. In addition, this iron oxide-based drug carrier possesses a low pH-activated release profile, which would accelerate drug release in the carcinoma cells and minimize non-specific drug release. Owing to these advantages, PMNTs promote the anticancer efficacy of PTX and clearly exhibit promising potential for using as high-efficiency insoluble drug delivery system in clinical applications.