Abstract: We introduce and study tetrahedron instantons. Physically they capture instantons on $\mathbb{C}^{3}$ in the presence of the most general intersecting codimension-two supersymmetric defects. In this talk, we will review instanton moduli spaces, explain the construction, moduli space and partition functions of tetrahedron instantons. We will also point out possible relations with M-theory index which could be a generalization of Gupakuma-Vafa theory.