The Orthos’ long reach makes it a shoe-in for a Combo-based Melee build. This kind of build relies on consecutive Melee strikes to build a multiplier, which boosts the weapon’s Damage the higher the combo counter goes. Mods like Body Count, Drifting Contact, and Gladiator Rush will serve to boost not only the combo timer (the time before the combo resets), but can also be augmented with Weeping Wounds, which will increase the Status Chance based on the Combo Multiplier.
The Orthos Prime can be built the same way as the Orthos, but replace Weeping Wounds with Blood Rush. It can also effectively be built for Status Chance / Damage using the dual-status mods rather than using Combo mods.
Both the Orthos and Orthos Prime will benefit greatly from the addition of a maxed-out Reach or Primed Reach mod, which increases their effective Range, thus hitting more enemies. Both weapons can also be pushed to 100% Status Chance, allowing every swing of the weapon to inflict a status proc, which will cause Damage over time.