Plant Muscadine vines in an area that is in full sun for most of the day and has loose soil that drains easily. According to Gerard Krewer of the University of Georgia, Muscadine vines will grow in almost any type of soil.
Build a sturdy trellis for the vine to grow along if one is not already present. The plants will need to be at least 12 feet apart.
Water deeply for the first two years, using at least a gallon of water per vine several times a week. Water mature vines only during extreme droughts and allow rainfall to do the rest.
Feed with a 10-10-10 fertilizer every six weeks from late April to early June. Spread the fertilizer in an 18-inch circle around the base of the vine, using one-quarter pound per plant.
Prune the vines each year during the dormant growth period between January and March. Cut back excess vines and any vines that are within two feet of the ground. Vines may bleed fluid during pruning. This does not harm the plant.
Keep the area around the plant well-weeded to prevent other growth from robbing the vine of nutrients.