Dr. Alex Cross (Tyler Perry) is a psychologist and police lieutenant who lives in the Indian village neighborhood of Detroit with his wife, Maria (Carmen Ejogo), their children, Damon and Janelle, and his grandmother, Nana Mama. Upon learning that Maria is pregnant with their third child, Cross considers accepting a job as an FBI profiler, but fears Maria's reaction, as it would require them to relocate to Washington, D.C. Meanwhile, a man called Picasso (Matthew Fox) participates in an underground mixed martial arts match, where he flirts with businesswoman Fan Yau (Stephanie Jacobsen). After brutally beating his opponent, Picasso is invited to Fan Yau's house in Grosse Pointe. There, he sedates, tortures, and kills her.
Police captain Richard Brookwell (John C. McGinley) calls Cross and his partner, Tommy Kane (Edward Burns), to the crime scene. On the way there, Cross tells Kane about Maria's pregnancy and the FBI's offer, and Kane reveals that he is secretly dating their colleague, Monica Ashe (Rachel Nichols). Investigating Yau's murder, Cross deduces that Picasso is a professional assassin, and finds a sketch left behind by Picasso revealing that his next target is a German businessman, Erich Nunemarcher (Werner Daehn). Cross, Kane and Ashe go to Nunemarcher's office, but he dismisses their claims. Picasso manages to enter the building, but is prevented from killing Nunemarcher by Cross, and escapes after being shot by Kane.
Analyzing a drop of Picasso's blood, Cross learns that Picasso is a psychotic former member of the Special Forces and that his real target is billionaire CEO Leon Mercier (Jean Reno). Cross informs Mercier that Picasso might be trying to kill him. Meanwhile, as revenge for their earlier interference, Picasso attacks Ashe, sedating and beating her; and later murders Maria with a sniper shot, leading both Cross and Kane to swear revenge against him. The detectives learn that Picasso is targeting Mercier at a conference and informs Brookwell, who isolates the area. However, Picasso is able to kill Mercier by firing a bazooka from a moving train. Cross and Kane chase after Picasso and corner him at an abandoned theater. Kane is injured in the car accident, Cross chases Picasso and Picasso hits him with a pipe, after that Picasso and Cross fight with Picasso pinning Cross. Picasso tells Cross he is going to enjoy killing him and takes out a syringe in order to paralyze Cross. Cross pulls out a little pocket knife and stabs Picasso in the shoulder. They then fall through the crumbling roof above a garage. Cross manages to grab hold of a bar with Picasso hanging on his leg. Picasso looks at Cross and says his final words to him "I made you!" Cross then knees him in his face while yelling "DIE!" Picasso then yells as he falls on to a red car, finally killing him and avenging Maria's death.