Research on multifunctional magnetic nanoparticles for biomedicines has experienced rapid growth because of the progressive advancements in nanotechnology and in modern biotechnology. However, the design of multifunctional surfaces on magnetic nanoparticles generally lacks a systematic approach. This article will try to unfold the complex chemistry in constructing a multifunctional surface, and layout a simplified guide for researchers to follow, particularly those from nonchemistry backgrounds. A number of design principles with critical rationales are to be introduced and followed by four main strategies: multifunctionality on a polymer chain, use of block copolymers, cocondensation of alkoxysilanes and of the secondary reaction on groups, with a particular reference to the use of alkoxysilanes. Nanoparticles of higher complexity are expected to be reported in the near future. These advanced systems are likely to be designed from some more logical, strategic mechanisms rather than the 'pick-and-mix' approaches we have seen in the last decade.