Can this really be attributed to his military genius

Whether you want to call it "genius," or just "talent," Alexander's military acumen certainly contributed. However:

were there underlying systemic factors

I would certainly say so, given that Alexander conquered exactly 1 pre-existing power,* and a few minor Thracian tribes. Certainly, he first had to put down several rebellions in and around Greece, but those were in territory that had already been pacified by his father, Phillip II. Phillip conquered most of Thrace, Ilyria, and the other regions north of Greece outright, and forced almost all of Greece (with the exception of Spartan Laconia) to surrender. Nominally, the Greek city-states remained independent members of the League of Corinth, but the treaty stipulated loyalty and support for Macedon and the ruling Argead Dynasty.

*maybe 1 significant state 3 minor polities in India that had already broken away from Persian control.

Aside from preventing Greek and Macedonian uprisings, Alexander's first military expedition after his father's assassination was against minor Thracian tribes in the Balkans. This secured his borders, but was hardly a contest for the Macedonians with all the wealth and resources of Phillip's expanded kingdom behind them.

Alexander is "the Great" because he conquered the Persian Empire. It hardly came quietly, but as Alexander captured territory, he was slowly taking control of a ready-made imperial administration. He simply placed Macedonian nobles at the highest rungs, even forgoing that step when the local nobility or Persian governors were particularly amenable.

Militarily, the unified nature of the territory Alexander was conquering meant that capturing just a few key locations and defeating large Persian armies in the field completely destabilized the capacity for the imperial forces to oppose his advance or provide assistance to individual cities. The Battle of the Granicus functionally wiped out Persian capacity to defend Anatolia, giving the Macedonians a foothold in Asia. Issus disrupted Persian Imperial mobilization for several years, giving Alexander free reign over the western 1/3 of the Empire, and Gaugamela completely shattered Persia's capacity to face Macedon in a pitched battle. Each victory gave Alexander progressively more access and control to Persia's territory. Plus, Egypt just invited him in since they had always resented Persian rule in the first place. Alexander actually faced significantly more individual pockets of resistance in Iran than he had in the west. By then, he was in control of the Empire's administrative centers, and the Iranians had difficulty organizing a sufficient force to combat the Macedonians.

Without a doubt, Alexander's famed charisma, military strategy, seasoned officers, and the newly-developed Macedonian phalanx all played their part in defeating Persia in a contest of arms. However, Alexander was also handed a series of systemic advantages by almost 70 years of Persian domestic politics.

After 130 years of failed attempts, Egypt seceded c.400 BCE, and during the 360s BCE (the tail-end of Artaxerxes II's reign), Anatolia and the Levant were gripped by a series of revolts and an Egyptian invasion. When Artaxerxes III came to power, he made retaking Egypt his first priority. To prepare, the king stripped the western Satraps and governors of their authority to maintain their own armies and settled treaties of friendship or non-aggression with all of the major Greek powers, including Macedon. This did lead to a successful reconquest of Egypt, but also the end of a decades old policy of Persian intervention to prevent any one power from gaining supremacy in Greece. That coincided with Phillip II's rapid expansion of Macedonian power, and by stripping the western governors of their armies, Artaxerxes inadvertently left them unprepared for Macedon's invasion.

Then, in 338 BCE, Artaxerxes III and most of his sons were assassinated by royal adviser called Bagoas. Bagoas installed the youngest prince as Artaxerxes IV, only to assassinate him as well after two years, shortly after Phillip's own assassination. Artaxerxes IV was a puppet ruler, and neither he nor Bagoas took significant action to repel Phillip's expeditionary invasion of northern Anatolia in 336. That fell to Darius III, a distant cousin of the Persian royal family handpicked by Bagoas who proved more formidable than the adviser expected when he had Bagoas executed. Darius did send an army to expel the Macedonians, but they were demoralized and in disarray following their own king's death and hardly an accurate representation of Macedon's capabilities.

Darius did not make any major policy changes to prepare for future conflict with Macedon. First and foremost, he was concerned with a new rebellion in Egypt and solidifying his own legitimacy. The first was dealt with relatively easily. With the massacre of Artaxerxes III's sons, and Artaxerxes III's own earlier policy of fratricide, the Persian chain of succession was pushed back to 2nd-4th cousins of Artaxerxes IV. There were dozens, if not hundreds, of potential claimants, so Darius III had to be cautious lest he face a coup. This and his earlier success against Macedon were probably driving factors behind his initial reluctance to call a full imperial draft to raise an army when Alexander invaded. Combined with Artaxerxes III's disarmament of the western satrapies, the Macedonians faced minimal resistance outside of the Battles of Issus and Gaugamela during the first-half of their invasion.