Macbeth's tragic flaw is ambition. Despite being showered by honors and titles by a grateful King Duncan, it's somehow not enough. He wants more, and is prepared to stoop to murder and treachery to get it.

Even so, Macbeth needs a little help to realize his ambitions. When it comes to actually following through, he gets cold feet about murdering Duncan and needs the assistance of his devious wife—who, if anything, is even more ambitious than he—to make it happen. Lady Macbeth cajoles her husband and questions his manhood when it appears that he's not prepared to go through with the murder plot. Had it not been for her, there's every reason to expect that Macbeth would've backed out at the last minute.

The Weird Sisters also play their part in encouraging Macbeth's ambitions. Their prophecies appear to provide a supernatural sanction to Macbeth's base treachery. Over the course of the play, Macbeth becomes so obsessed with the witches' prophecies that he starts to feel almost invulnerable. Not only did the witches prophesy that Macbeth would be king, they also predicted that only a highly unlikely event—the marching of Birnam Wood against him—would precipitate his fall. This seemingly unlikely prophecy only adds to Macbeth's confidence that he cannot be defeated by his enemies.

Macbeth's fatal flaw in the play is unchecked ambition, that is a desire for power and position, namely to be king, which is more important to him than anything else in life.  He is willing to give up everything that he has in his life in order to possess the crown to sit on the throne.

Yes, the ladies in the play do have something to do with it. The ladies include, the witches, the three in the beginning, as well as the queen of the witches, Hecate, and Lady Macbeth. 

What happens to Macbeth is a combination of events that lead to the opportunity to seize power.  He is influenced by the women in the play, the witches, who give him a prophecy that contains information that he will be king of Scotland. The witches don't give him a time table for his ascension to the throne, just that his future holds this for him.

"The witches in Macbeth are present in only four scenes in the play, but Macbeth's fascination with them motivates much of the play's action."  

He becomes so thrilled with the idea that he will be king, that he begins to think that he should be king right now.  Even though he has been a loyal servant to King Duncan, he becomes angry when he sees the king elevate his son Malcolm and proclaim him as the heir apparent to the throne of Scotland.

Macbeth is also influenced by his wife, Lady Macbeth.  In fact after Macbeth has thought about killing King Duncan, and had time to consider the witches prophecy, he decides that he doesn't want to kill the king.  Then once he tells his wife about the prophecy, she becomes so thrilled with the idea of being queen that she begs and pleads with him to convince him that he should kill the king, that he will have a singular opportunity when the king visits their home that evening.  It is perfect, she says, a once in a lifetime opportunity.  

"The extent of Lady Macbeth's power over her husband is debated. Some critics blame Lady Macbeth for precipitating Macbeth's moral decline and ultimate downfall. Others argue that, while Lady Macbeth appears to be increasingly guilt-ridden as the play progresses as evidenced by her sleepwalking episodes, Macbeth becomes increasingly murderous."

Then, she actually insults him, demeans him, accuses him of being less than a man if he doesn't have the courage to kill the king.  She is so vicious towards Macbeth that he finally agrees to kill the king. 

Once he does kill the king, he begins to unravel, mentally and emotionally.  As a king, he is stricken with a serious case of paranoia.  He believes that everyone is trying to kill him to take his throne, so he keeps murdering.  First he gets rid of Banquo, unfortunately, the killers don't kill Fleance, who is e Banquo's son.  Then after he goes to see the witches again, he is given another set of prophecies, and he decides to kill Macduff.  He sends murders to kill Macduff, he is not at home, so the murderers kill his entire family instead.

All of Macbeth's activities as king contribute to his doom or his undoing.  He is a terrible king, a tyrant who is feared. Malcolm, the rightful heir to the throne, joins forces with Macduff and the King of England who provides soldiers. Macbeth is confronted by Macduff, the only man capable of killing him, and he is killed and Malcolm is put on the throne. 

Macbeth's major tragic flaw is his ambition, as he himself reveals in his soliloquy in Act I, Scene 7:

I have no spur
To prick the sides of my intent, but only
Vaulting ambition, which o'erleaps itself
And falls on the other—

It is Macbeth's ambition that causes him to kill the King, an act that leads to his downfall. But Macbeth is also very trusting and easily persuaded. It never dawns on him until the climactic final scene that the witches might be misleading him by telling him he is essentially invincible. They are telling him what he wants to hear, and he never really questions them--indeed, he bases all of his actions on their prophecies. Lady Macbeth also easily persuades her husband to carry out the murder of the king, even when he has, after careful consideration, decided to put it off for awhile. Macbeth, while a very powerful man, allows himself to be led by others. That these "others" were female would have suggested to Shakespeare's audiences a weakness of will that they would have seen as an inversion of the natural order.