The 2011 winners Al Sadd SC are the only former champions in contention in the West and they are joined by a trio of Saudi clubs, a pair of Tehran giants and one side apiece from both the United Arab Emirates and Uzbekistan.
With four hotly anticipated match-ups to come over the weekend, the-AFC.com has selected five things to look out for as the non-stop action continues.
1. Can Al Soma rediscover the scoring touch?
Since making his AFC Champions League debut in 2015, Omar Al Soma has netted 18 times in 26 matches and, such is the Syrian's reliability in front of goal, it is rare for him to go two matches without scoring. However, ahead of Al Ahli Saudi FC's last 16 clash with Shabab Al Ahli Dubai, the striker has yet to find the back of the net in Qatar.
In truth, it has been a somewhat strange tournament for the Jeddah side since the resumption; they became the first team to book their place in the knockout rounds after winning their Matchday Three fixture against Al Shorta and have played without pressure since. Indeed, they were confirmed as Group A winners without having to pick up another point following a draw between Al Shorta and Esteghlal.
However, they go into the knockout rounds on the back of successive defeats and with their main marksman having drawn blanks in the two games in which he has played. A closer look at his numbers, meanwhile, shows that of the seven attempts he has had on goal, only one has been on target and, to date, he has looked less threatening than in previous campaigns.
While two games remains someway short of a drought, with the matches coming thick and fast in the 2020 AFC Champions League there is little doubt Al Ahli Saudi could do with Al Soma back to his lethal best, particularly as they are facing a side who have yet to concede in more than 270 minutes of action since the competition's resumption.
2. Masharipov vs Ghaedi
Two of the standout players since the AFC Champions League returned have been Pakhtakor's Jaloliddin Masharipov and Esteghlal FC's Mehdi Ghaedi, both of whom played key roles in helping their sides advance to the knockout rounds.
Uzbek international Masharipov, 27, displayed his talent with some stellar performances in the 2019 group stage but he has taken it up a notch this time round with two goals and two assists helping Pakhtakor advance to the knockout rounds for the first time since 2010.
Six years his junior, 21-year-old Ghaedi was the youngest player in the Esteghlal line-up in the must-win game against Al Ahli Saudi on Wednesday but produced an excellent display in which he scored the opener and played a part in the Tehran side's other two goals as they progressed to the last 16 in impressive fashion.
Both possess the ability to run past players and create chances for their teammates, as well as find the back of the net themselves, thus posing a major threat to opposition defences. With a place in the last eight on the line, Masharipov and Ghaedi could well be key to their respective sides' chances.
3. Hamdallah's time to shine?
With Abderrazaq Hamdallah playing no part in Al Nassr's Matchday Five and Six fixtures, the striker goes into Sunday's tie with domestic rivals Al Taawoun having scored in each of his past eight games on the Continent in a run dating back to last year's group stage tie against Zobahan.
The Moroccan has been among the most prolific goalscorers in Asia for some time yet the 2019 quarter-final remains the furthest he has been in the tournament, after injury ruled him out of El Jaish's run to the semi-finals back in 2016 and having failed to navigate the group stage with both Guangzhou R&F and Al Rayyan.
However, the 29-year-old may well feel that this is his year. In addition to bagging goals in his last eight AFC Champions League games he also finished top of the 2019-20 Saudi Pro League's scoring charts and netted a hat-trick when Al Nassr last faced off against Al Taawoun – a 4-1 victory back in August.
Al Nassr lost their final group game against Al Ain on Thursday but Hamdallah will retake his position as the focal point of the Riyadh side's attack on Sunday. If he continues his ruthlessness in front of goal then he, and his side, may have the opportunity to go deeper into the tournament than ever before.
4. Familiar foes meet again
When Al Sadd and Persepolis FC take to the field for their last 16 tie on Sunday it will be the seventh time in three seasons that the two sides have faced off, and the Qataris may feel they have a score to settle after it was the Iranians who denied them a place in the final in dramatic circumstances two years ago.
With Azadi Stadium packed to its capacity and the game on a knife edge as the clocked ticked down, Xavi advanced into the box to meet Jung Woo-young's delivery from the left, only to be denied by an incredible save from Alireza Beiranvand as Persepolis survived to reach the showpiece event.
The following year Xavi would play his final match before retiring at the same venue against the same opponents and, although Al Sadd lost on the night, they had already secured a place in the next round while Persepolis exited. Now, with the Spaniard in the dugout and Beiranvand departed, the teams get set to face off once more.
A much-changed Al Sadd lost their Matchday Six game against Sepahan but key personnel will be restored to the starting line-up against Persepolis, who have been one of the form teams in Qatar, winning three from four having yet to concede from open play. In what is arguably the standout tie of the round, Xavi and his charges will surely be desperate to avenge that 2018 heartbreak.
5. One-legged fixtures offer hope to all
In a change from the norm due to the unprecedented times worldwide, the AFC Champions League takes on a new format in the knockout rounds, with all fixtures to be played over one leg rather than two. This presents a situation where there is little margin for error.
Perhaps a prime example of how this could affect things came in the Matchday Six fixtures when, having lost all three of their games in Qatar – conceding eight and scoring none –Al Taawoun made Al Duhail pay for failing to take their chances as Mitchell Duke popped up with a late winner to stun the Qatari champions and seal a place in the next round.
With a star-studded line-up and strength in depth Al Duhail were a side many had tipped to go deep into the tournament but one off day and the dream was over. Such a scenario is likely to give teams such as knockout round debutants Al Taawoun and Pakhtakor, who have not reached the last eight since 2009, real hope that they can go even further.
While the move from two-legged fixtures to one will not mean form goes out the window it certainly provides extra intrigue going into the weekend's fixtures, and most likely adds pressure on the big boys ahead of what is sure to be a fascinating four games in the Round of 16.