Marco and Manny were paired together to think of a project to help create school spirit after the shooting. They bonded over the project, but had several obstacles in their friendship. Marco tried to make Manny realize that it was wrong to dump Spinner Mason, and later, after Marco had asked Manny to prom, he had to take back his invitation to go with Paige Michalchuk instead. The two gradually grew apart, but still occasionally interacted with each other, mainly through Marco's best friend and Manny's then boyfriend Craig Manning.
In Neutron Dance, Manny, Marco and Spinner Mason mainly hang out while Craig and Ashley Kerwin exclude them from making decisions about the band Downtown Sasquatch. Before a photo is taken for the band, Manny tells Spinner to change his shirt to another one, which Marco agrees with.In Bark at the Moon, Paige ditches her meeting with Raditch, and makes Manny take her place . She sits down next to Marco, commenting that she sometimes hates Paige. Mr. Raditch walks past her and Marco with a box, revealing that he has been relocated to another school. Manny and Marco enter the principal's office to discover to Ms. Hatzilakos is the new principal. She asks where Paige is, and Manny say, "I'm Paige for now". Ms. Hatlikaos tells them that she needs to create school spirit, and is allowing the school to perform J.T. and Liberty's play. She tells Marco and Manny that she needs both of them to look of a huge idea to help raise school spirit. Marco and Manny are later discussing ideas, and Chester gives them the idea to have a Cupid themed dance, where everyone is paired off by computer.
Later, during Raditch's farewell speech, Marco asks her in disbelief if she really dumped Spinner over a dance, saying he was heartbroken. Manny retorts that you can't dump someone if you were never going out, and that it wasn't working out. Their conversation is cut short by Mrs. Hatzilakos calling for Marco to give Raditch his farewell present. At the dance, Manny is paired with Danny Van Zandt, which angers her, as she wanted to be paired with Chester. She punches Marco in the arm, saying she was supposed to be with Chester. Marco says that the computer picks the matches, not him, and Manny angrily asks why would he do this to her. Marco tells her that Spinner loves her, and that she should stop being afraid of what happened last year with Craig, to take a chance.In West End Girls, Toby asks Manny to the prom, and before she can reject him, Marco interjects, saying that Manny is going to the prom with him. The two talk over the details of the prom, and Manny later tells Hazel that Marco is nearly her perfect date. However, Matt can't attend the prom with Paige, so Marco becomes Paige's date instead. Marco later apologizes to Manny, saying that Paige is heartbroken, but says that he'll vote for Manny for Prom Queen. This leaves Manny feeling angry, and commenting about her "sucky life".
Season 5In Weddings, Parties, Anything, Craig tells Marco about how Manny joined him and Ellie at The Dot, and Marco comments, "Cue the romantic train wreck." The next day, when they are packing up for their gig at a wedding, Marco first spots Manny in her sexy outfit, telling Craig to check her out. She later dances on stage next to Marco, who is playing the guitar.
In High Fidelity (1), Marco watches Manny and Darcy get into a fight. Marco gossips about the fight to Paige and Spinner.
In What's It Feel Like to Be a Ghost? (1), Manny attends a dinner party at Marco's house with Craig. When Manny is high on coke that she got from Craig, Marco tries to agree with her point about being a memorable actress, saying you'll need to get others to remember you. She accidentally knocks over a glass, which Marco cleans up.
In Rock This Town, Marco attends Manny's party.
In Notorious, Marco and Manny begin making eye-contact in the library, then Marco asks her if she is getting her daily Hollywood gossip fix, and then Manny tells him that she's looking for something to wear to the movie premiere, but everything was "light years" out of her price range. Marco tells her that he saw this amazing dress, that will flatter her body type. Manny then replies, "Holy cow, are you ever gay?" Marco laughs and then tells her that he can bore her by telling her the Italian Soccer Stats. Manny smiles and walks over to Marco and sits on his lap.
As Manny places herself on Marco's lap she asks him, if "it does nothing for him." Marco tells her that he's feeling "hot" and that he wouldn't be able to control himself. He also tells her that no matter how hard he tries, he doesn't feel any sexual tension to when Manny sitting on his lap. Manny tells him, that him being gay, must be hard-wired in his brain. Marco tells her that instead of instead of makeup and curves, he prefers the broad shoulders, and the bit of stubble type. Manny jokingly says that she should set him up with her aunt Miriam, and Marco jokingly replies to hook it up. Manny told him, that it must've been hard, being a homosexual, then Marco replies that it was when he first came out, he said that people weren't mean directly to his face, but he knew that people were talking about him behind his back judging him.
Marco then receives an e-mail containing a video of a remixed version of Manny being drunk and revealing herself on camera. Manny hears the video and gets upset, Marco notices her being upset and turns off the video. Manny says that it's bad enough that her flashing her boobs on camera is seen all over the world, but now there's a version that people can dance to. Marco tells her how hard it must have been, knowing that everyone has seen that video, of Manny and how hard it must have been. Manny explains to Marco that when she walks down the halls of the school, she doesn't care about the guys considering they're undressing her with their eyes, but when the girls look at her, they feel like she's there to piss them off. Marco tells her that if anyone else has been in Manny's position, then (s)he would be completely destroyed, but he tells her that she beat it, and that it's pretty hardcore. Manny tells Marco that she is who she is, and Marco tells her that she shouldn't apologize and people can say what they want.
Spinner is seen conveniently walking down the hallway when he sees Manny on Marco's lap, he then starts to look skeptical. He was going to tell Marco that he thought Marco was gay, but he decided to keep his mouth shut. Manny and Marco begin laughing, and Manny waves as Spinner left.
In Party Etiquette, Manny attends Marco's party.
- Manny had a conflict with two of Marco's best friends, Paige Michalchuk and Ellie Nash, although she eventually ended her conflict with both of them.
- They both kissed Craig Manning, who was another of Marco's best friends, but only Manny had a relationship with him.
- They were both friends with Hazel Aden.
- They both graduated from Degrassi: Marco in 2006 and Manny in 2007.
- Both Marco and Manny's parents were immigrants to Canada: Marco's parents Mr. Del Rossi and Louisa Del Rossi were Italian while Manny's parents Joseph Santos and Julietta Santos were Filipino.
- They both had problems with their fathers: Marco's father's homophobia made Marco reluctant to come out to him for several years, though he eventually came to accept it, while Manny's father was extremely controlling, though he later became much more understanding which led to a dramatic improvement in his relationship with Manny.
- They were both members of Downtown Sasquatch, though in Manny's case only temporarily.
- They were both Catholics.
- They were two of the six characters on Degrassi: The Next Generation to be followed after their graduation.
- Craig included songs about both of them on his album Of Two Minds: "Kissing in the Stairwell" (Marco) and "Thong Girl, Wrong Girl" (Manny).
- They both attended J.T. Yorke's memorial service at Degrassi in The Bitterest Pill.
- They were both members of the Degrassi Drama Department.
- They both prevented one of their best friends from committing suicide: Manny saved Darcy Edwards in both Standing In The Dark (2) and Live to Tell while Marco (and Craig) saved Ellie in Degrassi Goes Hollywood.
- While Manny was a very talented singer, it was revealed in Voices Carry (1) that Marco had a dreadful singing voice.
- They both had nose piercings.
- In The Bitterest Pill, Marco was upset by the death of Manny's close friend and ex-boyfriend J.T. Yorke.
- Paige slapped both of them.
- Manny had a conflict with Marco's friend Holly J. Sinclair.