Nano-scale materials are acquiring a leading role in the fabrication of new generation devices, especially for the practical application of molecular bi-stability. However, the preparation of purely bi-stable nano-objects without the use of surfactants/polymers remains a challenging task. Here, we present a new approach to prepare spin-crossover (SCO) vesicular nano-spheres with single-external diameters of approximately 100 nm using a CHCl₃–H₂O mixture. The nano-spheres are based on a series SCO complexes, [Fe(H₂Bpz₂)₂(dialkyl-bipy)] (H₂Bpz₂ = dihydrobis(1-pyrazolyl)borate, dialkyl-bipy = N⁴,N⁴′-dialkyl-(2,2′-bipyridine)-4,4′-dicarbo-xamide, alkyl = propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and cetyl), and are prepared through a self-assembly process that is similar to liposomal assembly, with the dialkyl-bipy moiety acting as the hydrophobic tail and the Fe(H₂Bpz₂) moiety acting as the hydrophilic head. This study reveals that the alkyl chain length plays a key role in the formation of these nano-spheres and the determination of their spin transition temperatures. The spin transition temperatures for the bulk materials are centered at around 160 K, and show a positive correlation with the alkyl chain length. Meanwhile, for the vesicular nano-spheres in the solid state, their transition temperatures are above room-temperature, and the correlation with the alkyl chain length is negative. These results provide an effective strategy for the design of new metal–organic materials for nano-technological applications.