Substance may refer to:

• Matter, anything that has mass and takes up space

• Chemical substance, a material with a definite chemical composition
• Drug, a chemical agent affecting an organism

• Substance (Blank & Jones album), 2002
• Substance (Joy Division album), 1988
• Substance 1987, a New Order album
• "Substance", a song by Haste the Day on the album Burning Bridges
• "Substance" (song), a 2022 song by Demi Lovato

• The Substance, 2024 film
• SubStance, an interdisciplinary journal on literature published by the University of Wisconsin Press
• Metal Gear Solid 2: Substance, an update of the video game Metal Gear Solid 2: Sons of Liberty

• Dravya, a term used in Jainism to refer a substance
• Ousia, term for substance in ancient Greek philosophy and Christian theology
• Substance theory, an ontological theory positing that a substance is distinct from its properties

• Substance use (disambiguation)
• Substance control (disambiguation)
• Substantial (rapper)