In the first featured story, Callahan travels to the picturesque town of Cape Coral, Florida to learn more about the disappearance of 29-year-old single mother, Lauren Dumolo, who was reported missing on June 19, 2020. In his quest to bring Lauren home, Callahan uncovers dark secrets and learns that certain people in Lauren's life might not have had her best interest at heart. Then, Callahan travels across the state to Ft. Lauderdale and immerses himself in the 2017 missing persons case of then 15-year-old Sophie Reeder, who snuck out from her father's home in the late evening hours on Friday, May 19.  When his investigation takes a turn into the shadowy world of the dark web, Callahan takes a deeper dive into the epidemic of human trafficking, and uncovers clues that Sophie might have fallen in the hands of those who perhaps groomed and targeted her.

In both cases, few clues are left behind, leaving Callahan to conduct boots-on-the-ground investigations into these disappearances. Speaking with law enforcement and the victim's family to understand the circumstances surrounding the fateful day they were last seen, Callahan works to reveal any leads or information that have been unearthed since they've been gone and asks viewers to call if they have information on the cases.

IN PURSUIT: THE MISSING also spotlights missing children cases from around the country, including: the July 10 disappearance of 10-year-old Breasia Terrell from Davenport, Iowa;  the August 4 disappearance of 12-year-old Jaylen Griffin from Buffalo, New York; the May, 2019 disappearance of then-16-year-old John Riser from Washtoukna, Washington; and the 2015 disappearance of then 5-year-old Ava Baldwin from San Antonio, Texas, which includes an age-progression photo provided by NCMEC to help guide the public on what she might look like now that she's 11.

John works with investigators to bring Frank Contreras into custody after he commits a terrible crime witnessed by a child; Cal takes on a heartbreaking case where authorities desperately need the public's help to identify a vicious criminal.

A family feud escalates to brutal violence and John joins police in pursuit of Top Ten FBI fugitive Eugene Palmer. Callahan immerses himself in one of the most brutal cases he's ever seen as he helps authorities track down Tamera Williams.

John joins the hunt for prominent community members Torin and Rena Smith, who absconded from justice after being accused of shocking crimes. Meanwhile, Cal pulls back the curtain on Carnell Spencer Lee Jr., a vicious criminal with a dark and menacing past.

John and investigators follow the trail of a chilling 911 confession that leads them to dangerous Nimrod Guerrero; when Frederick McCaskill leaves a survivor clinging to life, police and Cal work to make sure this criminal doesn't elude justice.

When an insidious sexual predator is discovered hiding in plain sight, John helps police in the pursuit of dangerous James Meece. And after a brutal home invasion, Cal goes into the field to help police track down the dangerous James Watts.

When an unthinkably violent criminal flees before his trial, John Walsh joins local authorities on the chase for Michael Waguespack; Cal uncovers hidden and painful truths in a Christmas Eve tragedy that sent police hunting for Miguel Angel Martinez.

John joins police on a strange and twisting missing persons case that turns fatal, sending investigators on the trail of Alejandro Castillo. And Cal takes on the case of Leticia Smith, a woman on the run from a terrible crime with nothing to lose.

After a vulnerable elderly man is brutalized in his rural home, John joins a manhunt for Derek Whisenand; then newlywed bliss turns into a vicious crime, so Cal goes on the trail of fugitive Arnoldo Jimenez.

When a double shooting leaves one woman dead and another clinging to life, John joins police on the trail of fugitive Lenell Kirby; Callahan takes on the murder of a dear Walsh family friend, Lindsay Harris.

When a costly mistake allows a criminal to escape justice, John steps in to help investigators in pursuit of felon Lester Eubanks. And Cal looks into the case of William Stanson, a supposed loving father to turned out to be and sexual predator.

A tragedy in a small community has John Walsh pursuing an outlaw named Jory Worthen, while John's son, Callahan, takes on the case of fugitive Derrell Demon Brown, an offender with a dark past.

John profiles fugitive Leroy Headley, who called 911 claiming to have shot his girlfriend, Anako Lumumba; Cal goes to Abilene, Texas, to learn more about a tale of predatory sexual abuse involving a predator whose own wife reports him to police.