The ability to alloy different elements is critical for property tuning and materials discovery. However, general alloying at the nanoscale remains extremely challenging due to strong immiscibility and easy oxidation, particularly for early transition metals that are highly reactive. Here, we report nanoscale alloying using a high-temperature- and high-entropy-based strategy (T∗ΔSmix) to significantly expand the possible alloys and include early transition metals. While high-temperature synthesis favors alloy formation and metal reduction, the high-entropy compositional design is critical to further extending the alloying to strongly repelling combinations (e.g., Au-W) and easily oxidized elements (e.g., Zr). In particular, we explicitly characterized a record 15-element nanoalloy, which showed a solid-solution structure featuring localized strain and lattice distortions as a result of extreme mixing. Our study significantly broadens available compositions of nanoalloys and provides clear guidelines by utilizing the less-explored entropic chemistry.