Two-dimensional (2D) semi-Dirac systems, such as 2D black phosphorus and arsenene, can exhibit a rich topological phase transition between insulating, semi-Dirac, and band inversion phases when subjected to an external modulation. How these phase transitions manifest within the quantum transport and shot noise signatures remain an open question thus far. Here, we show that the Fano factor converges to the universal F ≈ 0.179 at the semi-Dirac phase, and transits between the sub-Poissonian (F ≈ 1/3) and the Poissonian shot noise (F ≈ 1) limit at the band inversion and the insulating phase, respectively. Furthermore, the conductance of 2D semi-Dirac system converges to the contrasting limit of G/G 0 → 1/d and G/G 0 → 0 at the band inversion and the insulating phases, respectively. The quantum tunneling spectra exhibits a peculiar coexistence of massless and massive Dirac quasiparticles in the band inversion regime, thus providing a versatile sandbox to study the tunneling behavior of various Dirac quasiparticles. These findings reveal the rich interplay between band topology and quantum transport signatures, which may serve as smoking gun signatures for the experimental studies of semi-Dirac systems near topological phase transition.