The Cagayan Valley Region II is defined by the Cagayan River. The Province of Cagayan occupies the lower course of the river and the northeast corner of the island of Luzon (with a few offshore islets). Cagayan's area is 9,003 km². Its population was 952,000 (by the 2000 census) in 29 towns, of which Tuguegarao is the capital.

Archaeology indicates that the Cagayan Valley has been inhabited for half a million years, though no human remains of any such antiquity have yet appeared. The earliest inhabitants are the Agta, or Atta, food-gatherers who roam the forests without fixed abodes. A large tract of land has lately been returned to them. The bulk of the population are of Malay origin. For centuries before the coming of the Spanish, the inhabitants traded with Indians, Malays, Chinese, and Japanese. In the nineteenth century the prosperity found in tobacco cultivation caused many Ilokano to settle here. Tobacco is still a major factor in the economy of Cagayan, though a special economic zone and free port has been created to strengthen and diversify the provincial economy.

Cagayan has much to offer visitors: beaches, swimming, snorkeling, skin-diving, fishing in the river and the sea, hiking in primeval forest, mountain-climbing, archaeological sites, the remarkable collection of the provincial museum, the Callao Caves, and many fine churches. Even here there are fortifications built to protect the inhabitants from raids by the Mara.

The Philippine Republic's Region II, Cagayan Valley, contains two landlocked provinces, Quirino and Nueva Vizcaya. Both are relatively small in size (3057 km2 for Quirino, 4081 km2 for Nueva Vizcaya) and population (147,000 and 365,000, respectively, by the 2000 census). They are ruggedly mountainous and heavily forested. Nueva Vizcaya is the remnant of the southern province created when Cagayan Province was divided in two in 1839. They are ethnically and linguistically diverse, with a substrate of Agtas, Negritos who are food-gatherers with no fixed abodes, overlaid by Ilongots and others in a number of tribes, some of whom were fierce head-hunters (they have given up the practice), with the latest but largest element of the population being Ilokano.

Nueva Vizcaya comprises 15 towns; Bayombong is the capital. Agriculture in both has until recently consisted of slash-and-burn cultivation of corn and maize, though more stable cultivation of vegetables and fruits is becoming established. They produce logs and are trying to manage their forest resources so that production can be sustained indefinitely. They have deposits of gold, silver, copper, iron. Nueva Vizcaya has sand and clay.

At Balete Pass in Nueva Vizcaya the retreating Japanese under General Tomoyuki Yamashita dug in and held on for three months against the American and Filipino forces who eventually drove them out; the pass is now called Dalton Pass in honor of General Dalton, USA, who was killed in the fighting.

Nueva Vizcaya was probably named after Biscay (English: Biscay, Basque: Bizkaia) province in northern Spain. In this case there is some vexillological relationship between them, as the flag of New Biscay bears the arms of Biscay impaled on its seal.

The Cagayan Economic Zone Authority (CEZA) is in Santa Ana, Cagayan.

The province of Isabela is the richest in Cagayan Valley. It was the Top 10 Richest Province in the Philippines in 2011, being the only province of Northern Luzon to be included in the list.