Multiply twinned particles (MTPs) demonstrate great potential in the fields of catalysis, [1,2] high-strength alloys, [3] and thermoelectric conversion, [4] due to their unique catalytic, mechanical, and thermal/ electrical transport properties, respectively, which are induced by engineered facets, internal strain, and/or high-density twin boundaries. [5][6][7][8][9][10] Specifically, in terms of thermoelectric properties, twin boundaries are expected to have a minor influence on the carrier mobility ascribed to ordered atomic arrangement; by constructing high-density twin boundaries, phonon scattering would be enhanced effectively, providing a way in reducing the lattice thermal conductivity. [4,11,12] A notable example of MTPs is an icosahedral nanoparticle, which possesses fivefold twins, exposed low-surface energy planes, and irregular strain distribution. [13][14][15][16] Such unique characteristics open up a new route to the regulation and improvement of catalytic and thermoelectric properties. [4,17] Nevertheless, the precise regulation of icosahedral morphology is rather challenging. [18] In this context, much attention has been paid to understanding the formation mechanism of icosahedral nanoparticles, [19][20][21][22] given its importance to modulating the morphological characteristics and exploiting new material systems that can form into such morphology.Great success has been achieved in the synthesis of cubicstructured metal (e.g., Pt, Ag, Au, Cu) icosahedral nanoparticles based on well-developed chemical solution methods. [16,17] Accordingly, two mechanisms for icosahedron growth were explored and put forward: one is the successive growth from a tetrahedral unit via continuous twinning, [19,23] while the other is that particle agglomerates first have fivefold twins formed in the central regions and then gradually grow and develop into an icosahedron. [19,24] The latter process is commonly accompanied by a series of dynamic processes, including diffusion, coalescence, oriented attachment, and Ostwald ripening. [25,26] Importantly, considering that the dihedral angle between two adjacent {111} twin planes is 70.53° rather than 72°, [27] strain energy would be Multiply twinned icosahedrons possess a diversity of unique functionalities well-suited to various applications, such as thermoelectric conversion. Regarding chalcogenide icosahedron, an unconventional yet promising thermoelectric candidate, disclosing its growth mechanism is rather challenging. This study uncovers the formation mechanism of thermoelectric Cu 5+3x Fe 1-x S 4 (0 ≤ x ≤ 0.4) core-shell nano-icosahedrons, which is distinct from that of wellknown metal icosahedrons. Electron microscopy and molecular dynamics simulations reveal that the evolution into icosahedrons, stemming from the fivefold twin formation in the center of Cu 5 FeS 4 particle aggregates, is accompanied by the gradual formation of Fe-rich orthorhombic-structured core and Cu-rich cubic-structured shell, which provides a peculiar stress relaxation mechanism. Further ident...