Microwave-assisted chemistry is becoming very attractive in all areas of synthetic chemistry; it is fast, easy to operate, efficient in terms of energy consumption and environmentally friendly. However, a quantitative assessment of this chemical procedure with respect to other widely used chemical routes is lacking. Focusing in the preparation of iron oxide nanoparticles of comparable sizes, we have analyzed the performance of microwave-assisted synthesized nanoparticles compared to those obtained by the widespread thermal decomposition process of metal complexes. On the basis of a multidisciplinary experimental approach, we have unveiled that microwave-synthesized nanoparticles exhibit a surface reactivity significantly smaller than their thermal decomposition counterparts. We ascribe such dissimilarities to the different configurations of crystallographic faceting planes resulting from the particularities of both synthesis routes. We also show that the microwave route allows a direct stabilization of the particles in organic or aqueous media by using either steric or electrostatic stabilizers. A simplified life cycle analysis, as a preliminary framework toward nanoparticles eco-design, shows also a cost-effective positive balance for the microwave synthesis. Our results are of relevance for a broad range of applications including health, information storage, environmental remediation, sensors, or catalysis. © 2012 American Chemical Society.