Magnetic topological systems based on MnBi2Te4 have recently attracted significant attention due to their rich interplay between magnetism and topological electronic states. In this work, using density functional theory (DFT), we investigate topological phase transitions (TPTs) in Mn1−xGexBi2Te4 compounds with both ferromagnetic (FM) and antiferromagnetic (AFM) ordering under variations of spin–orbit coupling (SOC) strength and uniaxial strain along the c axis. We show that the emergence of a Weyl semimetal (WSM) phase requires the crossing of bands with opposite sz spin projections along the ΓZ direction. Modulation of SOC and strain can annihilate Weyl points via spin-selective hybridization, driving transitions into trivial or non-trivial phases. Furthermore, we demonstrate that a local asymmetry in Mn/Ge substitution – particularly at 37.5% Ge concentration (Mn0.625Ge0.375Bi2Te4) – can locally frustrate the AFM alignment between adjacent Mn layers and induce a WSM state, even in globally AFM systems, without external remagnetization. To optimize Weyl point separation and enhance the anomalous Hall effect (AHE), we propose partial substitution of Mn by Fe and Te by Se.