Topics covered in this series include the cost-of-living crisis, teen homelessness, racism, bulimia, being LGBTQ+, mental health, behavioral problems, young carers, gay fostering and adoption, elitism, knife crime, ADHD and the prioritisation of academic subjects over the arts in schools.

In February 2023, following the conclusion of the eleventh series, cast members Angela Griffin and Kym Marsh revealed that they were back filming on the set of the show.

Additionally, Kim's storyline features her struggling to maintain order at Waterloo Road in the wake of past events following a betrayal by her former lover and Deputy Head Linden King (Vincent Jerome) which almost caused her to lose her job.

The series increases its focus on Deputy Head Joe Casey (James Baxter) by expanding his home life, with a greater spotlight on his relationship with Mike Rutherford (Ryan Clayton) and their foster sons Dwayne (Thapelo Ray) and Zayne Jackson (Inathi Rozani).

You'll see what Mike's position is about fostering Dwayne and Zayne and taking them on, how that works throughout the series and the challenges that come with that", and noted that he and Baxter did a lot of research around the adoption process in preparation for the storyline.

[9] The character of Shola Aku (Chiamaka Ulebor) also features in a prominent young carer storyline beginning in the fourth episode, when it is revealed that she has been looking after her mother, who suffers from fibromyalgia.

Other returning students include Liam Scholes as Noel McManus, Lucy Eleanor Begg as Caz Williams, Chiamaka Ulebor as Shola Aku, Sahil Ismailkhil as Norullah Sayid, and Randi Agyare as Millie Adebayo.

On 18 April 2023, the BBC revealed that former cast member Jamie Glover would reprise his role as Andrew Treneman, Kim's former colleague and old flame who is now working as a representative of the Schools Against Knife Crime initiative and is sent to Waterloo Road following the events of the eleventh series' final episode.

Paul Bazely debuts as Ramesh Choudhury, Samia's father and the chair of governors at Waterloo Road, while Sia Kiwa features as Lisa Jackson, mother of Dwayne and Zayne who is a recovering alcoholic.

Hollie-Jay Bowes returns as Kelly Jo's mother and Nicky's sister Debs Raffety, having previously appeared in two episodes of series eleven.

The repercussions of the previous term’s stabbing continue to reverberate; airport-style metal detectors have been installed at the school entrance much to the consternation of the pupils who believe excessive force was used in the arrest of Danny Lewis and that the police are in fact the enemy.

Myles Massey, newly transferred to Waterloo Road from a football academy, decides to take part, but despite some shows of individual brilliance he eventually succumbs to a tackle by Dwayne Jackson, who he has been antagonising.

Later that same afternoon Danny receives a visit from Vinny with an offer that could see charges dropped, but after a meeting with Kim, he decides to go to the police and make a full confession.

Nicky Walters, in attendance to support Kelly Jo, lets slip that her niece has been given valium by her mother without a prescription resulting in a fight between the sisters later in the canteen which is witnessed by the school governors.

Kim is reminded by Val of her past as a champion of the arts when she was at the coalface as a teacher, and is encouraged by Andrew Treneman to go back to teaching some classes herself in order to better connect with the students.

Dean Weaver and Kelly Jo, out of the BU and back in the mainstream school on a trial basis find themselves in art class that Kim is taking.

A surprise OFSTED monitoring visit has Kim and the staff on edge as a negative report would see Waterloo Road put into special measures.

As the end of term approaches, the school is holding a day of sponsored sports events in aid of Chlo’s Wishing Foundation, the charity set up by Donte in memory of his late wife.

His mother messages him to say he has secured a trial with Leicester and not to do anything that might risk injury to his ankle, but Myles competitive nature gets the better of him and when he spots race leader Preston collapsed on the course, he carries on without helping and it’s left to Dwayne, in third place, to do the right thing and raise the alarm, whilst Kai administers CPR.

Whilst in hospital Preston receives a visit from a psychiatrist to help with his eating disorder, but he rejects the need for therapy and blames Kai for revealing his secret.

His mother Nicky meanwhile is racked with guilt over the theft of the computers, but is told to put it behind her by Danny who is at the school to talk about his experience with knife crime at the debut of Radio Waterloo Road.

He was a talented footballer and couldn't cope with not being able to play for a team anymore, he had pushed himself into taking part in a cross country race while not being fit and being first to come across Preston (Noah valentine) on the run who was lying unconscious on the ground suffering a heart attack.