$ \begin{aligned}解:(1)原式&=(-8)^2×(-8)^{2021}×0.5×0.5^{2021}× 0.25^{2021} \\ &=64×0.5×[(-8)×0.5×0.25]^{2021}=-32. \\ \end{aligned}$
$(2)因为3^m=5,3^{m-4n}=\frac{5}{81},$
$所以\frac{3^m}{3^{4n}}=\frac{5}{3^4},$
$所以4n=4,n=1,所以(9-10n)^{2023}=(9-10)^{2023}=-1.$