The South faced many problems during the Civil War, and it is easy to name three.
First, the South had the problem of having an agricultural economy. It is hard to win a war when all you produce is cotton, tobacco, and rice. The South had virtually no industrialization, and found it difficult to produce weapons or uniforms, for example. In spite of the fact that agricultural products can be turned into cash, plantations were not able to prosper because the plantation owners did not have enough manpower because of the disruptions of war and the enlisting of able men as soldiers. They could not produce enough to feed their slaves and make money. Some plantation owners enlisted themselves, and women were left to run the plantations. The women made a noble effort, but had insufficient resources to manage well.
A second problem the South had was that the war was mostly fought on in the South. A war that is fought on one's home ground is far more costly and painful than one fought on the ground of another. More civilians are sacrificed to the "cause," and the devastation and disruption are terrible.
A third problem for the South was organizational and political. The North had mechanisms in place with which to fight a war, with an established government and an established military. The South, while it was united on the matter of slavery, was not a cohesive country as the war began. It established a Confederacy and a military, but did not have the power of experience behind it.
Of the many challenges that confronted the South at the outset of the Civil War, there were some very significant hurdles that proved difficult to overcome. The North's industrial capacity proved to be overwhelming. An overwhelming majority of the factories resided in the North. This would allow the North to continue production of war-fighting materials, enabling them to fight a longer, more protracted conflict. Another major Northern advantage which proved to overwhelm the South was the control of the railway lines. Majority of the railway lines originated in the North, allowing the efficient transport of goods and soldiers to the front lines of various battles. At the time, railways were a new and efficient invention, and many of these lines remained loyal to the Northern government. Additionally, the Northern navy was able to successfully launch a blockade, which suffocated the South in preventing any foreign assistance. Finally, the Northern overwhelming advantage of population allowed a pool of soldiers to continually replenish military losses, allowing them a greater chance of success in a prolonged conflict.