Body-centered cubic (BCC) multi-principal element alloys (MPEAs) have emerged as promising structural materials for fusion reactors due to their exceptional resistance to irradiation-induced damage. Yet, the atomic-scale mechanisms underlying this superior performance remain elusive. Here, we employ large-scale atomistic simulations to elucidate how chemical complexity regulates helium (He) bubble evolution in W-based MPEAs. We find that reduced bubble pressure in chemically complex alloys suppresses dislocation loop punching, a primary driver of fuzz formation in pure W, thereby stabilizing the subsurface microstructure. This suppression is governed by two synergistic mechanisms: (i) thermodynamic heterogeneity that broadens defect energy distributions and lowers cluster binding energies, limiting the tendency formation of large loops, and (ii) lattice distortion arising from atomic size mismatch, which disrupts glide continuity and immobilizes loops near their nucleation sites. In addition, element-specific segregation patterns emerge around bubbles, reflecting kinetic asymmetries that may further stabilize local defect configurations. Collectively, these insights establish that suppressed loop punching via reduced bubble pressure is the central mechanism underlying enhanced radiation tolerance in W-based MPEAs. Beyond mechanistic understanding, our results provide clear design principles: thermodynamic tuning of defect energetics, controlled structural distortion to pin dislocation loops, and kinetic balance in solute selection. This work charts a pathway toward designing radiation-tolerant alloys for extreme fusion environments.