The principal physical limitation of a canonical tetra-stranded genome is electrostatics. Bringing four negatively charged polymer backbones into close proximity imposes a severe energetic penalty that cannot be addressed by local bonding alone. In this work, I develop an electrostatic framework for Q-DNA, extending classical Poisson–Boltzmann descriptions and ion-correlation theories to a four-strand geometry. I analyze how multivalent cations, polyamines, and molecular crowding reshape the electrostatic free-energy landscape and can induce effective attraction between strands. I predict distinct ionic signatures and identify environmental regimes in which tetra-stranded architectures become electrostatically favorable relative to duplex DNA. This analysis establishes electrostatics as the dominant gatekeeper for the existence of canonical four-stranded genomes. Keywords: Q-DNA, electrostatics, Poisson–Boltzmann theory, ion condensation, multivalent cations, molecular crowding