In Rest on the Flight into Egypt, Caravaggio presents a serene scene filled with rich colors. The figures of Mary and the infant Jesus are depicted resting under a tree, surrounded by lush foliage. The warm tones of the earth contrast with the cool greens of the leaves, creating a harmonious balance.

The light falls dramatically on the figures, emphasizing their peaceful expressions. This painting is executed in oil on canvas, showcasing Caravaggio's signature use of chiaroscuro. The contrast between light and shadow enhances the three-dimensionality of the figures. The dimensions are approximately 130 x 170 cm, making it a sizable work that draws the viewer in.

The careful attention to detail in the textures of the clothing and the natural elements is notable. Caravaggio painted this work around 1597, during a time when he was exploring themes of religious narrative. This painting is significant as it captures a moment of tenderness and humanity in a biblical story. Interestingly, it is believed that the artist drew inspiration from his own experiences of travel and hardship.

The work is currently housed in the Museo di Capodimonte in Naples, Italy.