Regina is now on another mission, involving a facility located close to a town called Edward City. A major anomaly has caused the whole island to be transported back in time to the era of the dinosaurs, along with all the human inhabitants. Regina also has a new ally, Dylan, who is playable through half of the game and has a strange connection to the events on the island. The player's character changes at specific points in the game. The goal is to rescue any survivors and retrieve data on Third Energy.
In a departure from the survival horror theme of the original game, Dino Crisis 2 is more shoot 'em up-oriented. The player character always runs, eliminating the need for a run button. A secondary weapon (machete, stun gun, firewall, chain mine and shock gun) can also be carried, and more weapons have been added (hand gun, shotgun, solid cannon, flame launcher, sub-machine gun, heavy machine gun, anti-tank rifle, missile pod, rocket launcher, needle gun, aqua grenade). Besides changes to the gameplay, also introduced are new species of dinosaurs and lizards, such as the Triceratops, Allosaurus, Mosasaurus, Plesiosaurus, Inostrancevia, Oviraptor and Giganotosaurus.
The game also adds "extinction points" and "combo points" which allows the player to buy ammo (which is no longer scarce) and weapons, as well as to unlock hidden features when the game is finished. Weapons can be bought at glowing computer terminals which are scattered throughout the island.
Some of the features include Extra Crisis mode, which has two minigames: "Dino Colosseum", where the player faces a procession of dinosaurs in turn, (similar to Survival Mode seen in many fighting games) and "Dino Duel", a battle mode where players are able to pit dinosaurs against each other. All 11 Dino Files that are collected throughout the game access bonus levels after completing it once.
- Dylan Morton
- Paula - (non-playable) - One of the mysterious hostile survivors of Edward City apprehended by Regina. She acts rather timid around Dylan, and is also somehow a part of his life. She plays a significant part in the story, and appears randomly throughout.
- David Falk - (non-playable) - One of Dylan's team members who always appears cheerful and raises the morale of the team. He wears a cowboy hat. Though his fighting style is not as strong as Dylan's, his friendliness is his greatest asset. He gets eaten by an Allosaurus.
- Oviraptor - Their small size makes these particular dinosaurs hard to get a good shot at. They scamper and attack in groups. Some will spit poison, some will jump-kick Regina/Dylan. Players will have a better chance of surviving if they continue to move around and attack.
- Triceratops - two Triceratops are featured in one of the on-rail shooter parts of the game, where Dylan and Regina have to escape a parental team of angry Triceratops that wrongfully thought that the two killed their young. They use a jeep with a mounted rifle on the back in order to fend the enraged parents off.
- Mosasaurus - an alligator-like creature that can, at times, seem to appear from nowhere. Regina battles them in the underwater section of the game.
- Plesiosaurus - The first time this species is encountered is when Dylan and Regina leave the Jungle for the first time and the player must shoot them as they are attacking the ship. As long as the player has good aim they're not particularly hard to bring down. They are also encountered in the docks at the Third Energy Facility, but can be killed with one shot from a Heavy Machine Gun. A Plesiosaurus also appears in the submerged Third Energy reactor room, where it serves as the stage's boss.
- Inostrancevia - Inostrancevia possess armor-like scales over most of their body, making them highly resistant, but not invincible, to weapons fire. The best way to defeat it is to flip the Inostrancevia over onto its back using the "Chain Mine" weapon. This exposes the creature's soft underbelly which can be fired at, damaging and ultimately killing it.
- Allosaurus - It is a large predator, something of a middle ground between the small and agile Velociraptor and the slow, powerful Tyrannosaurus, serving as the most powerful non-boss enemy in the game. Its head is heavily armored, capable of being highly resistant gunfire up to and over pistol rounds and buckshot rounds. To maximize this advantage, the Allosaurus uses its agility to keep its head constantly in front of its prey. Towards the end of the game, it is an Allosaurus that kills David Falk. It also makes an appearance in the game Namco ✕ Capcom as an enemy.
- Giganotosaurus - Regina faces this huge dinosaur boss in the Missile Silo near the very end of end of the game. Repelled and eventually knocked unconscious by flames and their accompanying fumes, the Giganotosaurus later awoke to find Regina next to the missile. Breaking the metallic structure in order to reach her, the missile collapsed onto the ground and exploded. Somehow surviving the explosion unharmed, the Giganotosaurus moved down-river into the Noah's Ark Plan's timegate complex it came from, where it challenged Dylan. It was finally killed when a satellite in communication with the complex fired a powerful beam directly onto the creature, creating a deep chasm in the ground.