If this list is only related to running bosses, then Doedre the Vile can easily become the most difficult boss on the list. You can check the feasibility of the soft-core version here, and hard-core players will have to overcome this huge obstacle, otherwise they may lose several hours of progress.

Doedre will cause crazy physical or chaotic damage based on her current element injection, which the player can control. The arena is small, there are no creeps to prevent the flask from regenerating, and her damage can weaken with a single blow. Before solving this terrible boss, take advantage of the POE Currency.

To this day, Atziri, the Queen of Val, has almost no structures. The boss created his own copy to reflect the user's injury, which caused most meta-builds to be unable to safely kill her.

The summoner, the construction based on the life value and the clearest speed will make it difficult to complete the Hall of Grandmasters Map. This map is so difficult that most players purchase Atlas from other players.

Although this is not a single boss, the master lobby matches players with characters who have purchased a master support package. In fact, this is the boss's gloves. PvP scaling has also been enabled, causing any summoner build to die immediately. Most characters will evade or obscure, making most matching-based versions obsolete. If you think rogues are tough, try to complete the master hall.

In the deepest part of Delve, players can find Aul. Without modifiers, the boss seems to be a knight with no special mechanics, and he loves cold damage very much.

When you face him, Aul will have modifiers that make him stronger. The farther you are in Delve, the stronger Aul and his minions will be. Players will need to buy POE Orbs PS4 to keep Darkness' DoT away, while facing the boss who can freeze you immediately and kill you in two blows. Combined with the ridiculous health pool (expandable to the depth of Delve), Aul easily became the toughest boss on the path of exile.