A Save the Children report has found more than a quarter of a million children living in those areas face the daily threat of barrel bombs, air strikes and shelling as well as starvation.
Families have told their stories to charity workers on the ground.
Parents have spoken about the psychological impact on their children as well as the dire consequences of being deprived of food, basic medicine and clean water.
One mother told Save the Children: "I've been burning pieces of cloth to create heat".
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"We don't have any food, no fuel or clothes for the children," she said.
"I haven't been able to even store any food or supplies. My child has been crying for a piece of bread since the morning."
Another mother told the charity's workers: "My husband died in a shell attack, here on this corner".
"He died and left me with two orphans," she said.
"The situation is becoming very bad. We don't have any bread or any sugar. We'd prefer to die that continue living like this."
A boy told Save the Children he was cold and had nothing to keep himself warm.
"There is no wood or anything," he said.
"We have no shoes, slippers or clothes. We have no warm hats or heaters or gloves."
The report said children were being forced to eat boiled leaves and animal feed for their one daily meal and teachers were setting up schools in basements to protect pupils from bombs.
Residents described how snipers tried to shoot at anyone who leaves, trapping the population in an "open-air prison".
Despite the UN Security Council passing six resolutions since 2014 calling for unobstructed humanitarian access in Syria - one every four months - the number of people living under siege has more than doubled in the last year.
According to Save the Children, recent efforts to deliver aid are welcome but it is only a fraction of what is needed.
Some vital medicines, fuel and high nutrition food are being removed from convoys, and people are still not allowed to leave for medical treatment.
Humanitarian adviser Sarah Ireland said children were dying from lack of food and medicines in parts of Syria just a few kilometres from warehouses piled high with aid.
"They are paying the price for the world's inaction," she said.
"Families interviewed for this report spoke of sick babies dying at checkpoints, vets treating humans and children forced to eat animal feed as they cower in basements from airstrikes."
"Enough is enough. After nearly five years of conflict in Syria, it's time to end the sieges."
