Before tired Nathan can finally rejoin his longing family, Dan has turned up and secured himself a temporary stay on account of his burnt-down restaurant, where he lived, but may have torched it. Chase is happy but exhausted on account of running the bar and an intense sex life with Alex. As if nocturnal baby care exhaustion wasn't bad enough for Julian and Brooke, his studio project only seems to bring debt and her boys fashion label fails to get financed, but her father Ted Davis actually turns up for the twins' christening. Clay's exhaustion is diagnosed medically serious. Chris Keller got engaged by Haley's music label under an alias, immediately antagonizes Alex but proves himself an genius producer.

Chase confides only in Chuck his plan to move Alex's things into his place. They ignore Chris Keller made her an offer for a career-boosting, national tour. As even the psychiatrist Clayton grudgingly consults can't properly diagnose his problems, Nathan decides with support from Jamie and Haley to attend in his pace the European forum for international sports talent scouting. This allows Dan to prolong his stay and carry out a mysterious plan. Julian warns Brooke that Victoria tries trough him to sabotage her father's apparently business-wise sound project to co-found a male fashion label.

Chase is heartbroken after Alex's desertion to take the tour Chris Keller advised, yet overcomes his bitterness toward Keller, who pleads her artist temperament was a lost case from the start. Julian is near despair about the unused studio until a TV series project comes within reach. Alas coaxing the studio proves tragically incompatible with paternal duties, while Brooke charms investors for her boys fashion project with her father. Clayton's problem is worse then thought, as Quinn discovers spying on him. Haley now runs Karen's café, but her cook is sick, so Dan steps in but that costs some bigot customers, and a mystery competitor opens across the street.

Julian is even more shattered than Brooke, who gives him the silent treatment, over having forgotten baby son Davis in his car. Although the boy is alright, Brooke leaves with the twins until Haley talks sense into her. Drunk, Chase enjoyed a wild night with a shameless flirtster but shyly wriggles out of continuation in the morning, on account of Alex's memory, only to find her with Chris Keller the next day. Dan and Jamie enjoy camping but dreaded Nathan's return is likely to mean grandpa's exit. After Dan scares away Clay's dealer, he comes clean to Quinn and consults Dr. Alvarez, who promises recovery but only after residential therapy.

Chase bravely bares Chuck's absurd, imitative adoration for 'cool', actually neglectful Chris Keller and stands by the ingrate knave when his father Wade Scolnic finally visits, but discards Chase as if a random babysitter. Nathan is missing since his flight home from Europe days ago. After cocky Keller helps activating Tree Hill PD officer Stevens, Haley finds Dan's cash stash and suspects a horrible crime. Julian can't forgive himself even now his loved-ones do, blames himself for bullying by strangers and picks a bar-brawl to get a 'bloody good' beating. Pushed by Dan and Quinn, Clay checks in for residential therapy with Dr. Alvarez, keeps dismissing 'mere talk' as therapy, but decides against signing out after meeting shy Logan, a neglected orphan boy who hangs around the rehab clinic.

Dan enlists Julian to help in his search for Nathan. Mouth fills Clay in about Nathan, as Haley explains Nathan's disappearance to Jamie. Brooke gets an idea of how to bring patrons to an empty Karen's Café, and Chris Keller confronts Chase about Tara.

Haley seeks help from Lucas as Nathan makes an escape attempt. Brooke comes face-to-face with Xavier. Julian uncovers evidence that assists Dan in his search for Nathan. Clay makes a connection with another patient.

Haley receives news of a possible tragedy. Dan's search for Nathan leads him back to his dark past. Clay has a breakthrough in his treatment. Brooke and Julian deal with Xavier. Chase's concern for Chuck pushes him to his limits.

Brooke and Julian take new measures to protect their family. Skills helps Mouth get to a turning point, and Chase faces consequences for defending Chuck. Clay reaches a new understanding with Logan.

Dan, Julian and Chris Keller attempt to rescue Nathan. Brooke's conflict with Xavier escalates. Quinn and Clay revisit the past.

Nathan's practically safe return causes general joy. The only downside is Dan's condition, probably terminal, but the whole family is in a forgiving mood while reminiscing, only Lucas refuses to come. Julian is welcomed as a hero and hears Brooke survived Xavier's attack, then stands by her as a paternal visit proves too good to be truly non-business. Clay goes to Sara's parents, who have raised Logan, and gets them to agree to let his son be invited home with him and Quinn.

Julian finally sells his One Tree Hill series concept to a studio and is hired to complete the script. Clayton and Quinn, who welcomes Sara's memory to, patiently win Logan's trust to become a warm; close family. Chase gets over his confidence crisis as bar manager just before he's offered a chance to buy Tric from Karen on the boat burning day. After Julian scolds father-in-law a useless father and Brooke 'surprises' her divorced parents back in bed, an unexpected business move makes up for a lot.

In the final chapter of One Tree Hill, the tenth anniversary of Tric brings old faces and new possibilities for the Tree Hill family. To celebrate the 10th anniversary they host a concert at Tric that includes Gavin Degraw. Julian buys Brooke's childhood home for them to live in. Nathan and Haley celebrate their 10th wedding anniversary.