This intimate piece features a dimly lit location and just a few figures to allow us to focus on the key theme. We find the baby revealed in the centre of the artwork, and the overall composition is essentially a simplified version of the Adoration of the Shepherds. Here he only includes the Holy Family, and none of the accompanying shepherds from other versions. This provides a very different atmosphere and underlines the sensitive nature of this painter. As a religious man himself he would have enjoyed receiving such commissions, as these paintings were also a way for him to celebrate his own faith and remind him of the key themes of the Bible. He was tasked with producing work for Hospital de la Caridad in Illescas, Spain, and there were to be four different paintings in total, namely The Madonna of Charity, The Coronation of the Virgin, The Annunciation and The Nativity. He would already have covered some of these themes in previous artworks but would have considered how the four pieces could be displayed together in a consistent style. By this stage he also had a studio with assistants who could help out on some of the less critical elements of his paintings.

El Greco is known to have used the services of his son specifically for some of these artworks, in a supporting role. The initial contract was then completed and a further artwork, St Ildefonso, was commissioned on top. El Greco received regular work in this manner from religious institutions who wanted to fill their buildings with wonderful depictions of Christian themes. Normally these would be places of worship but in this case it was for a hospital in the small town of Illescas. Much of the continent's wealth was held by religious groups during this period in European history and so inevitably most artists would be required to focus on scenes suitable for their followers, even though some might have preferred to tackle other genres from time to time. El Greco himself completed many portraits too, and these could be quick projects for wealthy locals who wanted to be remembered by future generations. The artist's oeuvre focuses on those two genres, with little else though it must be remembered that he was also fairly religious himself and so would have been more willing to meet his patron's requests.

In order to meet the requirements of the altarpiece, it was decided that Nativity would be completed as a round artwork, sometimes called a tondo. These were common in Italian art but very few came from El Greco's studio, making Nativity an interesting addition to his career. During the Renaissance and Baroque eras it was not uncommon for a commissioned artwork to be delivered in an unusual shape in order to fit the desired location, as many had intended destinations. Today we would rarely see this because rectangular paintings can be moved around and placed almost anywhere, so long as there is enough space for them. Whilst this piece was in oils, some other artists used tempera or fresco techniques and it was only later on that oils would be used by almost all artists across Europe. This method came from Northern Europe and was slowly taken on by Italian painters, with El Greco himself choosing to make the switch as his career progressed.