The first wife of Nicomedes III of Bythinia was the Cappadocian Princess Nysa, daughter of the Monarchs Ariarathes VI of Cappadocia and Laodice of Cappadocia.

By Nysa, Nicomedes III has two sons who (Nicomedes IV of Bithynia, Socrates Chrestus and a daughter called Nysa).

Nicomedes III and Nysa are distantly related as they hold lineage from the Seleucid dynasty, the Antipatrid dynasty and the Antigonid dynasty.

When Nicomedes is asked to provide troops for Roman Statesman Gaius Marius’ war on the Cimbri and Teutons in transalpine Gaul in 104 BCE, he turns down the request, declaring: "All those eligible for military service in my kingdom have been robbed by the Roman tax-farmers and sold into slavery".

The kingdom of Cappadocia has maintained a faithful allegiance to Rome since the Roman victory at Magnesia in 190.

Ariarathes VII of Cappadocia had in his first years reigned under the regency of his mother Laodice, the eldest sister of the King Mithridates VI of Pontus.

During this period the kingdom had been seized by King Nicomedes III of Bithynia, who married Laodice.

Nicomedes is soon expelled by Mithridates, who restore Ariarathes to the throne, but when the latter objects to his father's assassin and ally of Mithridates, Gordius, the Pontian monarch has him killed and puts in his place a son of his as Ariarathes IX Eusebes Philopator.

Since the new king is only eight years old, he is put under the regency of Gordius.

He is early overthrown by a rebellion by the Cappadocian nobility, who replace him with Ariarathes VIII of Cappadocia, whom Mithridates promptly expels, restoring Ariarathes IX.

Mithridates is however deprived of his advantage over Nicomedes by the Roman Senate's instructions to Lucius Cornelius Sulla, as proconsul, to install a pro-Roman king here in 96.

Sulla becomes the first Roman magistrate to meet a Parthian ambassador, Orobazus, and by taking the seat between the Parthian ambassador and Ariobarzanes I of Cappadocia (the center seat being the place of honor), he seals, perhaps unintentionally, the Parthian ambassador's fate.

(Orobazus is executed upon his return to Parthia for allowing Sulla to outmaneuver him.)

It is at this meeting he is told by a Chaldean seer that he will die at the height of his fame and fortune.

This prophecy is to have a powerful hold on Sulla throughout his lifetime.

After the short period of direct Pontic rule, the brief restoration of Ariarathes VIII and an attempted instauration of a republic, Sulla seats on the throne a man chosen by the Cappadocians, who reject the idea of a Republic: the choice falls on Ariobarzanes I Philoromaios.

Supported by Sulla, Ariobarzanes will be in on-and-off control of a kingdom that is now considered a Roman protectorate.

Nicomedes had made himself master of Paphlagonia for a time.

After the deaths of his first wife and father-in-law, in order to have a claim on Cappadocia, Nicomedes had married his former mother-in-law as his second wife Laodice, who had fled to him when King Mithridates VI of Pontus (Laodice’s first brother) endeavored to annex the country.

With Laodice's two sons Ariarathes VII and Ariarathes VIII dead, Nicomedes III brings forward an impostor as a claimant to the throne; but the plot is detected.

The Roman Senate refuses to recognize the claim, and requires Nicomedes III to give up all pretensions to Cappadocia and to abandon Paphlagonia.