The first few years of his kingship were relatively peaceful, but soon King Mithridates VI of Pontus (the maternal grand-uncle of Nicomedes IV), one of Rome's greatest enemies during the late Republic, began harassing Bithynia's borders.

As such, two powerful Romans, Gaius Marius and the consul Lucius Cornelius Sulla aimed at a command in the region.

After marching on Rome and outlawing Marius, Sulla sailed east and fought Mithridates VI on several occasions over the next three years, and finally in 85 BC, Mithridates VI sued for peace, and was allowed to retain his kingship in Pontus after paying a heavy fine.

[9] It is unknown if a sexual relationship existed or was only a story told by his opponents, and Caesar vigorously denied its truthfulness.

Rome's old enemy Mithridates VI of Pontus had other plans for Bithynia, however, and Nicomedes IV's death and bequeathal led directly to the Third Mithridatic War.