Nick is descended from a line of creature hunters known as Grimms, who have the responsibility to protect the rest of mankind from the creatures who are known as Wesen. Aunt Marie also tells him that the trailer she brought contains information and equipment to help him in his task. gives Nick a small antique key and tells him to protect it with his life as "they" want it. With help from Monroe, a Blutbad he met while working on case, and Rosalee Calvert, a Fuchsbau, Nick deals with crimes involving several different types of Wesen ranging from the bear-like Jägerbars to the rat-like Reinigen.

Nick is being reunited with his mother, Kelly Burkhardt briefly. Sean Renard wakes Juliette from her coma with a potion, revealing himself to be a half-Zauberbiest and a Royal. The potion is causing Sean and Juliette to become dangerously obsessed with each other. This requires all of Rosalee's apothecary skills to resolve. Juliette is unable to remember her relationship with Nick. Nick is forced to explain to Hank about Wesen and that he is a Grimm. Adalind conducts affairs with both Sean Renard and his brother, Eric, to become pregnant and trading the baby with Stefania Vaduva Popescu, the Queen of the Schwarzwald Gypsies, for the return of her powers. Eric conceives a plan to capture Nick and force Sean to return to Europe using the zombies of Baron Samedi to create chaos in Portland. The season ends with Nick in a coffin in the first stage of a Cracher-Mortel victim: paralysis with a death-like appearance.

Under the effects of the Cracher-Mortel toxin, Nick causes the plane carrying him to Europe to crash, killing Baron Samedi. A residual effect of the Cracher-Mortel toxin, however, causes Nick's endurance to be increased along with his strength. Juliette, with her new-found knowledge of the Wesen world, enthusiastically joins Nick, Hank, Monroe, and Rosalee in their adventures. Adalind's pregnancy continues as she goes through the Contaminatio Ritualis with the help of Stefania, and Captain Renard realizes that the rumored royal baby being offered for sale could be Adalind's. Captain Renard arranges for the assassination of his half brother, Eric, who is replaced in the royal hierarchy by his cousin, Viktor. Monroe proposes to Rosalee, and she happily accepts.

Nick, Juliette, Hank, and Trubel go straight to Nick's home from Monroe and Rosalee's wedding after Trubel tells them that Captain Renard was shot, despite everyone being in shock that Nick has lost his Grimm powers. While Nick is powerless, he uses Trubel in Wesen cases. Nick and Juliette consider living a normal life together instead of Nick trying to get his Grimm powers back, but Juliette tells Nick he needs to get his powers back. Trubel decides Nick doesn't need her as much after he gets his powers back, so she decides to go to Philadelphia with Josh Porter. Monroe is kidnapped to have his fate decided by a tribunal for his marriage to Rosalee, as well as befriending a Grimm. Monroe is found guilty and sentenced to death, but he is saved by Nick and the gang. Soon after Nick gets his powers back, Juliette turns into a Hexenbiest as a side effect. She decides to try to get rid of it instead of telling Nick.

The fifth season of “Grimm” sees Nick and his friends facing new challenges, as a group of Wesen terrorists emerges in Portland and begins to wreak havoc. As Nick and his allies race to stop the terrorists, they also face personal challenges, including the discovery that Juliette has become a powerful hexenbiest, and the return of Nick’s long-lost love interest, Adalind. Meanwhile, the Royals continue their efforts to gain control of Portland and its supernatural population, with Captain Renard playing a pivotal role in their plans. The season culminates in a dramatic showdown between Nick and his allies and the Royals, as Nick finally discovers the truth about his family and his place in the world of the Wesen.

With the arrival of the mysterious and powerful demon Zerstorer, Nick must fight to protect not just his loved ones but all of humanity. Alongside his friends Monroe, Rosalee, and Hank, Nick must also navigate the dangerous politics of the Wesen world, where old grudges and power struggles threaten to tear everything apart. As Zerstorer’s power grows stronger, Nick and his allies travel to different realms and encounter new and dangerous creatures. But with the fate of the world at stake, they cannot afford to fail. Along the way, Nick is forced to make difficult choices and confront the darkest parts of himself, all while keeping his loved ones safe and protecting the innocent. In the climactic final battle, Nick faces off against Zerstorer in an epic showdown that will determine the fate of the world. With everything on the line, Nick and his allies must use all of their strength, courage, and wits to save humanity from destruction.